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Two early papers expressing conflicting views on the occurrence of effective immune attack against cancers stimulate an analysis of the gradual development of an understanding of tumour biology. This understanding has led to the development of the strikingly effective check point blocking and CART anti-cancer immunotherapies, and the promise of more widely applicable therapies based on T cell attracting genetically engineered monoclonal antibodies., (© 2022. The Author(s).)

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed.

Multiple myeloma (MM) exhibits significant heterogeneity in its presentation, genetics, and treatment response. Despite therapeutic advances, some patients continue to relapse early (ER, <18-months) and rapidly cycle through therapies. Myriad prognostic factors have been identified and incorporated into risk stratification models; however, these produce discordant, often three-tiered outputs that fail to identify many patients destined for ER. Treatment strategies are increasingly focused on disease biology and trials enriched for high-risk (HR)MM, but consensus on the minimum required testing and a succinct, specific, and clinically meaningful definition for HRMM remains elusive. We review the risk-factors, definitions, and future directions for HRMM., (© 2024 Wiley Periodicals LLC.)

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention.

Allergy to Polistes dominula (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of P. dominula venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample. Three products with P. dominula venom and one product with a venom mixture of American Polistes species showed a comparable band pattern in SDS-PAGE as the reference sample and the bands of the major allergens phospholipase A1 and antigen 5 were assignable. The other product, which consists of a mixture of American Polistes species, exhibited the typical band pattern in one, but not in another sample from a second batch. All annotated P. dominula allergens were detected at comparable levels in LC-MS/MS analysis of products containing P. dominula venom. Due to a lack of genomic information on the American Polistes species, the remaining products were not analyzed by this method. The major Polistes allergens were present in comparable amounts in the majority, but not in all investigated samples of venom preparations for VIT of P. dominula venom allergy. [ABSTRACT FROM AUTHOR]

Epidemiologic data suggest an increased prevalence of pediatric food allergies and intolerances (FAIs) during the last decades. This changing scenario has led to an increase in the overall healthcare costs, due to a growing demand for diagnostic and treatment services. There is the need to establish Evidence-based practices for diagnostic and therapeutic intervention that could be adopted in the context of public health policies for FAIs are needed. This joint position paper has been prepared by a group of experts in pediatric gastroenterology, allergy and nutrition from the Italian Society for Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and the Italian Society for Pediatric Allergy and Immunology (SIAIP). The paper is focused on the Diagnostic Therapeutic Care Pathway (DTCP) for pediatric FAIs in Italy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: To evaluate the clinical outcome of lightened version of egg oral immunotherapy (OIT) and to analyze egg allergen component-specific antibody levels during short up-dosing with egg white powder and maintenance by egg in daily diet., Patients and Methods: Eighteen egg-allergic children received egg powder with short up--dosing and they maintained tolerance using egg in daily diet. Seventeen egg-allergic children served as a control group. Component-resolved analysis of serum immunoglobulin E (IgE), IgA1, IgA2, and IgG4 levels were determined at inclusion, after up-dosing and after 1 year of immunotherapy. Skin-prick tests were performed at inclusion and after 1 year of therapy., Results: All 18 patients in the egg OIT group were successfully desensitized. Desensitization was achieved on average in 4.5 months. In the control group, only two children tolerated egg in oral food challenge after 1 year. Of the measured immune markers, smaller wheal diameters in skin-prick testing, reduction in component-specific IgE levels, and increase in component-specific IgA1, IgA2, and IgG4 levels were associated with desensitization., Conclusion: A lightened egg OIT is effective and safe in children with egg allergy. Increase in all egg component-specific IgA1, IgA2 and IgG4 levels and decrease in all egg component--specific IgE levels were observed after 12 months of OIT.

The South West Oncology Group's 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear. Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy. Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35–49) RFS at five years in the control arm and 60% RFS (53–67 95% CI) in the maintenance arm (p < 0.0001). Only 16% of patients in the treatment arm received all of the scheduled maintenance courses of BCG. The study's seminal results correlate with contemporary systematic review and have guided international guidelines. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) immunotherapy is a first-line treatment for selected cancers, yet the mechanisms of its efficacy remain incompletely understood. Furthermore, only a minority of patients with cancer benefit from ICB, and there is a lack of fully informative treatment response biomarkers. Selectively exploiting defects in DNA damage repair is also a standard treatment for cancer, spurred by enhanced understanding of the DNA damage response (DDR). DDR and ICB are closely linked-faulty DDR produces immunogenic cancer neoantigens that can increase the efficacy of ICB therapy, and tumour mutational burden is a good but imperfect biomarker for the response to ICB. DDR studies in ICB efficacy initially focused on contributions to neoantigen burden. However, a growing body of evidence suggests that ICB efficacy is complicated by the immunogenic effects of nucleic acids generated from exogenous DNA damage or endogenous processes such as DNA replication. Chemotherapy, radiation, or selective DDR inhibitors (such as PARP inhibitors) can generate aberrant nucleic acids to induce tumour immunogenicity independently of neoantigens. Independent of their functions in immunity, targets of immunotherapy such as cyclic GMP-AMP synthase (cGAS) or PD-L1 can crosstalk with DDR or the DNA repair machinery to influence the response to DNA-damaging agents. Here we review the rapidly evolving, multifaceted interfaces between DDR, nucleic acid immunogenicity and immunotherapy efficacy, focusing on ICB. Understanding these interrelated processes could explain ICB treatment failures and reveal novel exploitable therapeutic vulnerabilities in cancers. We conclude by addressing major unanswered questions and new research directions., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Immunotherapy for lung cancer has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer immunotherapy. Method: On 1 July, 2022, the authors identified 2,941 papers on lung cancer immunotherapy by the Web of Science and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top papers) as well as major journals on lung cancer immunotherapy. After that, recent research hotspots were analyzed based on the latest publications in major journals. Results: These 2,941 papers were cited a total of 122,467 times. “Nivolumab vs. docetaxel in advanced non–squamous non–small–cell lung cancer” published in 2015 by Borghaei H et al. was the most cited paper (5,854 citations). Among the journals, New England Journal of Medicine was most influential. Corresponding authors represented China took part in most articles (904) and papers with corresponding authors from the USA were most cited (139.46 citations per paper). Since 2015, anti–PD–(L)1 has become the hottest research area. Conclusions: This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on thousands of publications, and further suggests future research directions. Moreover, the results can benefit researchers to select journals and find potential collaborators. This study can help researchers get a comprehensive impression of the research landscape, historical development, and recent hotspots in lung cancer immunotherapy and provide inspiration for further research. [ABSTRACT FROM AUTHOR]

The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome. In few patients, the disease undergoes phenotypic differentiation between 7 and 14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, comorbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1β, IL-6, IFN-γ, and TNF-α) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed "COVI-Flu." Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1–2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1–3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation. [Display omitted] • Undefined nodal RT indications for non-ALND patients with 1–2 positive SLN. • Undefined nodal RT indications when PST transforms cN1 disease into ypN0. • Undefined nodal RT indications for N + 1–3 mastectomized patients. • Optimal combinations of RT and immunotherapy are as yet unknown. • PBI after second BCS should be proposed for re-irradiation in low-risk patients. • Hyperthermia should be made available for superficial breast cancer recurrencesrecurrences. [ABSTRACT FROM AUTHOR]

Background: radiotherapy is one of the major treatments for lung cancer and has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer radiotherapy. Method: On August 31, 2022, the authors identified 9868 articles on lung cancer radiotherapy by the Web of Science (Science Citation Indexing Expanded database) and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top-papers) as well as top-journals on lung cancer radiotherapy. After that, the authors analyzed the recent research hotspots based on the latest publications in top-journals. Results: These 9868 papers were cited a total of 268,068 times. "Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer" published in 2017 by Antonia et al. was the most cited article (2110 citations). Among the journals, New England Journal of Medicine was most influential. Moreover, J. Clin. Oncol. and Int. J. Radiat. Oncol. Biol. Phys. was both influential and productive. Corresponding authors represented the USA (2610 articles) and China mainland (2060 articles) took part in most publications and articles with corresponding authors from Netherlands were most cited (46.12 citations per paper). Chemoradiotherapy was the hottest research area, and stereotactic body radiotherapy has become a research hotspot since 2006. Radiotherapy plus immunotherapy has been highly focused since 2019. Conclusions: This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on 9868 relevant articles, and further suggests future research directions. The researchers can benefit in selecting journals and in finding potential collaborators. This study can help researchers gain a comprehensive picture of the research landscape, historical development, and recent hotspots in lung cancer radiotherapy and can provide inspiration for future research. [ABSTRACT FROM AUTHOR]

Introduction and aim. Over the last few decades, there has been tremendous progress in the treatment of cancer. Unfortunately, anti-cancer therapies, although necessary and increasingly effective, still carry many side effects. One of these effects is the chemobrain -- cognitive disorders resulting from strong chemotherapy. The aim of this paper is to review available knowledge of chemobrain. Material and methods. The paper reviews articles available in the PubMed medical database, searched with the phrases "chemobrain", "chemobrain cancer" from the years 2015-2023 which are reviews, systematic reviews or meta-analyses. 41 results were obtained, of which 13 articles were used for the final analysis after the selection of papers strictly related to the issue of chemobrain. Analysis of literature. The occurrence of chemobrain is associated with impaired cognitive abilities, problems with concentration, and memory loss. It may occur only during treatment or persist even after its completion. According to the data, chemobrain occurs much more often as a complication of traditional chemotherapy than in the case of immunotherapy. The mechanism of chemobrain formation is not known. A combination of oxygen radical production and cytokine dysregulation is suspected as an inducer of this complication. Chemobrain treatment strategies remain under development. At the moment, non-pharmacological methods are used in the treatment, such as regular physical exercise, mental exercise, or a diet including omega-3 fatty acids. Pharmacological treatment is still under development and research. Conclusion. Chemobrain is a medical complication that can have a serious psychological impact on patients undergoing anti-cancer therapy, so further research is needed to better understand the mechanism of this phenomenon, which will allow the development of new treatments and possible ways to prevent the occurrence of chemobrain. [ABSTRACT FROM AUTHOR]

BackgroundThere is a crosstalk between gut microbiota (GM) and cancer immunotherapy (CI). The purpose of this study is to use bibliometric analysis to identify the highly cited papers relating to GM/CI and explore the research status and development trends of the GM/CI research.MethodsA literature search regarding GM/CI publications from 2012 to 2021 was undertaken on July 4, 2022. The article titles, journals, authors, institutions, countries, total citations, keywords, and other information were extracted from the Science Citation Index Expanded (SCIE) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package and VOSviewer were used for bibliometric analysis.ResultsA total of 665 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2018. The United States and China had the most publications and made great contributions to this field. Th5e Univ Texas MD Anderson Canc Ctr and Univ Paris Saclay were absolutely in the leading position in GM/CI. The most influential authors were Zitvogel L and Routy B. Frontiers in Immunology had the most publications and Science had the most total citations. Historical direct citation analysis explained the historical evolution in GM/CI. Highly cited papers and high-frequency keywords illustrated the current status and trends of GM/CI. Four clusters were identified and the important topics included the role of GM and antibiotics in CI, the methods of targeting GM to improve CI outcomes, the mechanism by which GM affects CI and the application of ICIs in melanoma. “Tumor microbiome”, “proton pump inhibitors” and “prognosis” may be the new focus of attention in the next few years.ConclusionThis study filtered global publications on GM/CI correlation and analyzed their bibliometric characteristics, identified the most cited papers in GM/CI, and gained insight into the status, hotspots and trends of global GM/CI research, which may inform researchers and practitioners of future directions.

The aim of this research is to use bibliometric analysis to investigate the status and patterns of the 100 most frequently cited publications regarding the cytotoxic T-lymphocyte-associated protein (CTLA-4) research for cancer. The articles published on the topic were retrieved from the core collection database of Web of Science and PubMed using the Medical Subject Heading (MeSH) of "CTLA-4" from 1986 to December 6, 2020. The selected articles were examined and the bibliometric data compiled based on the number of citations, the author's name, journal, publication year, institution, country, and co-occurrence keywords. 4,874 eligible papers were returned from the Web of Science Core Collection Database and PubMed. The citation frequency ranged from 2372 to 205, with a median of 460, and the top cited paper had 2372 citations. The journals with the most papers were Cell (n = 8, 3541 citations, Impact Factor (IF) = 41.577) and Journal of Experimental Medicine (n = 7, 2716 citations, IF = 10.790). Most of the published papers were from the United States of America (USA) (41.8%). A total of 485 institutes and 29 countries were involved in these 100 articles. There were 1192 authors and the author with the highest number of papers was the Nobel Prize winner, Professor James P. Allison (17 papers; 8700 citations). CTLA-4 blockade was the most frequent keyword (42.1%), followed by metastatic melanoma (4.26%). This work presents an important bibliographic source and can be saved as a reference for future medical health research on the function of CTLA-4 in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction and aim. Local allergic rhinitis (LAR) patients are diagnosed based on the presence of clinical symptoms such as rhinorrhea, sneezing, and nasal itching with negative skin prick testing and negative serum-specific immunoglobulin E (sIgE) assessment for the specific allergen. Our paper aims to provide insight into the pathogenesis of LAR, the local production of IgE in the nasal mucosa, and challenges associated with the investigation of this phenomenon. The current state of knowledge and future research perspectives on the management of LAR patients are presented. Material and methods. This review included literature searched using Medline, Embase, and PubMed. A total of 53 articles were identified initially and after applying the exclusion criteria 38 articles (32 original and 6 reviews) were selected for the analysis of literature. Analysis of literature. Based on the assessed studies, not only patients with allergic rhinitis (AR) show the presence of nasal IgE for the specific allergen (Mites, pollen, and molds), but also those who are classified in the non-allergic rhinitis (NAR) and LAR groups. The results support the hypothesis stating that NAR/LAR patients may have local production of IgE at the level of nasal mucosa following local inflammation due to exposure to specific allergens. Conclusion. The possibility to assess the local synthesis of sIgE and other mediators can help in adding allergen immunotherapy (AIT) to the management protocol of LAR patients and may provide new insights into phenotypical and endotypical classification of AR. [ABSTRACT FROM AUTHOR]

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy 1,2 . However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-α gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Increasing evidence indicates the involvement of B cells in the pathogenesis of multiple sclerosis (MS), but their precise roles are unclear. In this Review, we provide an overview of the development and physiological functions of B cells and the main mechanisms through which B cells are thought to contribute to CNS autoimmunity. In MS, abnormalities of B cell function include pro-inflammatory cytokine production, defective B cell regulatory function and the formation of tertiary lymphoid-like structures in the CNS, which are the likely source of abnormal immunoglobulin production detectable in the cerebrospinal fluid. We also consider the hypothesis that Epstein-Barr virus (EBV) is involved in the B cell overactivation that leads to inflammatory injury to the CNS in MS. We also review the immunological effects - with a focus on the effects on B cell subsets - of several successful therapeutic approaches in MS, including agents that selectively deplete B cells (rituximab, ocrelizumab and ofatumumab), agents that less specifically deplete lymphocytes (alemtuzumab and cladribine) and autologous haematopoietic stem cell transplantation, in which the immune system is unselectively ablated and reconstituted. We consider the insights that these effects on B cell populations provide and their potential to further our understanding and targeting of B cells in MS.

In this study, a bibliometric analysis was carried out to identify the most influential clinical studies and research trends on anti-programmed cell death 1/programmed cell death 1 ligand 1 (anti-PD1/PDL1) immunotherapy. On January 1, 2022, we used Web of Science to identify the 100 most frequently cited papers on clinical studies investigating anti-PD1/PDL1 immunotherapy, and extracted the following data: publication year, source title, country/region, institution, and the total number of citations. The research design and area were classified independently by the authors. Subsequently, we carried out a bibliometric analysis to determine the trends and identify the major journals on anti-PD1/PDL1 immunotherapy. The authors analyzed the current research hotspots based on papers published in major journals from 2020 to 2021. These 100 papers were cited a total of 138,840 times, and the median number of citations was 899.5 (range: 341–7,983). "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer" by Topalian et al. had the highest number of citations (7,983 times). New England Journal of Medicine had the highest number of top-cited papers (40 papers), average citations per paper (1,558.3 citations), and rate of top-cited papers (65.6%). Authors from the USA contributed most of the papers (76 papers). Lung cancer (30 papers, 46,422 citations) and melanoma (20 papers, 30,881 citations) were the most cited research areas. In summary, anti-PD1/PDL1 has become standard treatment for various cancer, while adjuvant anti-PD1/PDL1 therapy is currently a research hotspot. New England Journal of Medicine was identified as the most influential journal in this area. Non-small cell lung cancer and melanoma are the most well-studied cancers, while nivolumab and pembrolizumab are the most commonly investigated anti-PD1/PDL1 antibodies. Further studies are warranted to identify effective predictive biomarkers or models, clarify the molecular mechanism of combined therapy, and establish optimal therapeutic strategies. This study may assist researchers in obtaining a comprehensive impression of the landscape and current trends in anti-PD1/PDL1 immunotherapy and gain inspiration to conduct further studies. [ABSTRACT FROM AUTHOR]

Newer treatments for multiple myeloma (MM) have improved response rates and survival for many patients. However, MM remains challenging to treat due to the propensity for multiple relapses, cumulative and emergent toxicities from prior therapies and increasing genomic complexity that arises due to clonal evolution. In particular, patients with relapsed/refractory MM often require increased complexity of treatment, yet still experience poorer outcomes compared with patients who are newly diagnosed. Additionally, several patient subgroups, including those with extramedullary disease and patients who are frail and/or have multiple comorbidities, have an unfavorable prognosis and remain undertreated. This review (based on an Updates-in-Hematology session at the 25th European Hematology Association Annual Congress 2020) discusses the management of these difficult-to-treat patients with MM.

Objective: This study aims to analyze the 100 most cited papers and research trends on stereotactic body radiotherapy (SBRT). Methods: We used Web of Science to identify the 100 most frequently cited papers on SBRT on September 29, 2021 and extracted the following data: publication year, source title, country/region, organization, total citations, and average number of citations per year. The research type and research domain were classified independently by the authors. Then we carried out a bibliometric analysis to determine the trends in research on SBRT. Results: These 100 papers were cited a total of 26,540 times, and the median number of citations was 190 (range, 138-1688). "Stereotactic body radiation therapy for inoperable early stage lung cancer" by Timmerman et al. had the highest number of total citations (1688 times). International Journal of Radiation Oncology, Biology, Physics published the largest number of papers (37 papers), followed by Journal of Clinical Oncology (13 papers). The USA contributed the most papers (67 papers), followed by Canada (18 papers). Primary lung cancer (33 papers, 10,683 citations) and oligometastases (30 papers, 7,147 citations) were the most cited research areas. Conclusions: To the best of our knowledge, this is the first bibliometric analysis of the most frequently cited papers on SBRT. Our results provide insight into the historical development of SBRT and important advances in its application to cancer treatment. Early-stage non–small-cell lung cancer and oligometastases were the most cited research areas in the top 100 publications on SBRT, and SBRT combined with immunotherapy was a hot topic in the past few years. This study is helpful for researchers to identify the most influential papers and current research hotspots on SBRT. [ABSTRACT FROM AUTHOR]

Human intratumoral immunotherapy (HIT-IT) is under rapid development, with promising preliminary results and high expectations for current phase III trials. While outcomes remain paramount for patients and the referring oncologists, the technical aspects of drug injection are critical to the interventional radiologist to ensure optimal and reproducible outcomes. The technical considerations for HIT-IT affect the safety, efficacy, and further development of this treatment option. Image-guided access to the tumor allows the therapeutic index of a treatment to be enhanced by increasing the intratumoral drug concentration while minimizing its systemic exposure and associated on-target off-tumor adverse events. Direct access to the tumor also enables the acquisition of cancer tissue for sequential sampling to better understand the pharmacodynamics of the injected immunotherapy and its efficacy through correlation of immune responses, pathologic responses, and imaging tumor response. The aim of this article is to share the technical insights of HIT-IT, with particular consideration for patient selection, lesion assessment, image guidance, and technical injection options. In addition, the organization of a standard patient workflow is discussed, so as to optimize HIT-IT outcome and the patient experience., (©2021 American Association for Cancer Research.)

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (~10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Pembrolizumab, a monoclonal antibody targeting programmed cell death-1 (PD-1), is approved as a therapy for unresectable or metastatic melanoma. Immunotherapy-associated pneumonitis is an uncommon event., Patient Concerns: A 73-year-old man was admitted to our hospital with a history of melanoma on the left side of the face (resected in December 2012) and metastasis to the left lung upper lobe (resected in November 2016). Recurrence of metastasis to the bilateral lungs and left pleura was detected in April 2018. A complete response was achieved following treatment with pembrolizumab, with lower limb rashes the only adverse events occurring during therapy. The patient was readmitted in March 2019 with a productive cough, shortness of breath, and mild fever, and sputum culture identified Escherichia coli., Diagnosis: A diagnosis of pneumonia was made, and although cough and shortness of breath responded to ceftazidime and levofloxacin, but fever and poor appetite persisted. Computed tomography showed no improvement in the bilateral lower lobe lesions. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. The response to prednisone confirmed the diagnosis., Interventions: The patient first received ceftazidime and levofloxacin, but the symptoms persisted. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis., Outcome: Complete resolution of the bilateral lung lesions occurred after 45 days of prednisone therapy., Conclusion: This case report highlights that both pneumonitis and bacterial pneumonia can occur as complications of anti-PD-1 immunotherapy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

As in other regions, the incidence of atopic dermatitis in Latin America has been increasing in recent years. Although there are several clinical guidelines, many of their recommendations cannot be universal since they depend on the characteristics of each region. Thus, we decided to create a consensus guideline on atopic dermatitis applicable in Latin America and other tropical regions, taking into account socio-economic, geographical, cultural and health care system characteristics. The Latin American Society of Allergy Asthma and Immunology (SLAAI) conducted a systematic search for articles related to the pathophysiology, diagnosis and treatment of dermatitis using various electronic resources such as Google, Pubmed, EMBASE (Ovid) and Cochrane data base. We have also looked for all published articles in Latin America on the subject using LILACS (Latin American and Caribbean Literature on Health Sciences) database. Each section was reviewed by at least two members of the committee, and the final version was subsequently approved by all of them, using the Delphi methodology for consensus building. Afterward, the final document was shared for external evaluation with physicians, specialists (allergists, dermatologists and pediatricians), patients and academic institutions such as universities and scientific societies related to the topic. All recommendations made by these groups were taken into account for the final drafting of the document. There are few original studies conducted in Latin America about dermatitis; however, we were able to create a practical guideline for Latin America taking into account the particularities of the region. Moreover, the integral management was highlighted including many of the recommendations from different participants in the health care of this disease (patients, families, primary care physicians and specialists). This practical guide presents a concise approach to the diagnosis and management of atopic dermatitis that can be helpful for medical staff, patients and their families in Latin America. [ABSTRACT FROM AUTHOR]

Pioneer work by Prof. Cossart among others, studying the interactions between pathogenic bacteria and host cells (this discipline was termed Cellular Microbiology), was fundamental to determine the bacterial infection processes and to improve our knowledge of different cellular mechanisms. The study of bacteria-host interactions also involves in vivo host immune responses, which can be manipulated by bacteria, being these last potent tools for different immunotherapies. During the last years, tumour immunotherapies, mainly the use of antibodies that target immune checkpoints [checkpoint inhibitors (CPI)], have been a revolution in oncology, allowing the treatment of tumours otherwise with very bad prognosis. In the same direction, bacteria inoculations have been used from long to treat some cancers; for example, non-muscle-invasive bladder cancer can be successfully treated with the bacterium Bacillus Calmette Guerin (BCG). More recently, it has been shown that microbiota could determine the success of CPI immunotherapies and intense research is being performed in order to use bacteria as immunotherapy tools due to their ability to activate the immune system. In this context, to expand the knowledge of the bacteria-immune system interactions will be fundamental to improve tumour immunotherapies., (© 2020 John Wiley & Sons Ltd.)

Background: Immune checkpoint inhibitors have revolutionised the oncological landscape in the last few years. Possible applications include the treatment of hepatocellular carcinoma and cholangiocarcinoma. Unfortunately, new immune-related adverse effects have been associated with the use of these agents and the liver is one of the organs most frequently involved., Aims: To provide a general overview of the potential impact of immune checkpoint inhibitors on the liver METHODS: We reviewed the literature and abstracts/presentations on immune checkpoint inhibitors at most relevant hepatology meetings over the last 5 years., Results: The role of immune checkpoint inhibitors has been investigated both for the treatment of viral hepatitis and primary liver cancer. Hepatocellular carcinoma and chronic hepatitis B show the greatest potential for treatment with these drugs in the near future. However, immune-related adverse events involving the liver are a growing concern related to their widespread use., Conclusions: Immune checkpoint inhibitors represent an exciting new class of drugs with currently limited application in malignant and non-malignant liver disease. Caution must be exercised on the emergence of potentially severe immune adverse reactions., (© 2019 John Wiley & Sons Ltd.)

Simple Summary: Proton pump inhibitors are frequently used in cancer patients to alleviate some symptoms, epigastric pain or heartburn. However, acid suppression decreases the absorption of some oral-targeted anticancer treatments (tyrosine kinase inhibitors, CDK4/6 inhibitors) and induces changes in the gut microbiome. Recent data are showing that these interactions have important clinical impacts and medical oncologists and patients must be aware of these possible interactions. Multikinase inhibitors (MKIs), and particularly tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs), are currently some of the major breakthroughs in cancer treatment. Proton pump inhibitors (PPIs) revolutionised the treatment of acid-related diseases, but are frequently overused for epigastric pain or heartburn. However, long-term acid suppression from using PPIs may lead to safety concerns, and could have a greater impact in cancer patients undergoing therapy, like bone fractures, renal toxicities, enteric infections, and micronutrient deficiencies (iron and magnesium). Moreover, acid suppression may also affect the pharmacokinetics of drugs (at least during acid suppression) and decrease the absorption of many molecularly-targeted anticancer therapies, which are mostly weak bases with pH-dependent absorption. This type of drug-drug interaction may have detrimental effects on efficacy, with major clinical impacts described for some orally administrated targeted therapies (erlotinib, gefitinib, pazopanib, palbociclib), and conflicting results with many others, including capecitabine. Furthermore, the long-term use of PPIs results in severe alterations to the gut microbiome and recent retrospective analyses have shown that the benefit of using CPIs was suppressed in patients treated with PPIs. These very expensive drugs are of great importance because of their efficacy. As the use of PPIs is not essential, we must apply the precautionary principle. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician. [ABSTRACT FROM AUTHOR]

Introduction and aim. Melanoma is a malignant neoplasm of melanocytic origin, the development of which largely depends on the influence of UV radiation. Its development is preceded by the appearance of a melanocytic (dysplastic) nevus. Treatment of patients with metastases to distant organs remains the greatest challenge, as the results of treatment in patients with stage IV melanoma are still unsatisfactory. The progress in systemic therapy of generalized melanoma is based on two mechanisms: molecularly targeted treatment and non-specific melanoma immunotherapy, which is characterized by a unique action - instead of inducing the destruction of tumor cells, it strengthens or stimulates the anti-tumor response of the patient's immune system. Immunotherapy uses ipilimumab and Nivolumab that uses the natural ability of the immune system to eliminate primary cancer cells. It inhibits the binding of the cytotoxic T-4 antigen to its ligands, thereby enhancing T-cell response and tumor resistance. The aim of the study was a presentation of the role of monoclonal antibodies in the treatment of melanoma. Material and methods. During the preparation of the presentation 4 databases (PubMed, Google Scholar, Sciencedirect, Medscape) were searched for studies science publications from march 2019 to March 2023 in English. The search terms were: „ipilimumab in melanoma" „ monoclonal antibodies in melanoma treatment" "nivolumab in melanoma" in the title or abstract or as keywords. A total of 660 references, excluding duplicates, were identified. Analysis of literature. Studies show that nivolumab in combination with ipilimumab reduced the risk of death by 45%, compared to ipilimumab monotherapy. The two-year overall survival rate was 64% for nivolumab in combination with ipilimumab, 59% for nivolumab monotherapy, and 45% for ipilimumab monotherapy. Conclusion. Monoclonal antibodies against various immune checkpoints have revolutionized the treatment of metastatic and inoperable melanoma. The combination of two monoclonal antibodies, e.g. ipilimumab with nivolumab, is much more effective than the use of these antibodies in monotherapy. [ABSTRACT FROM AUTHOR]

We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Individuals with constitutional mismatch repair-deficiency syndrome (CMMR-D) are characterised by early occurrence of colon cancer, haematological malignancies, and brain tumors (malignant gliomas, high-grade gliomas) in childhood, adolescence, and early adulthood. High mutational tumor burden is typical of glioblastoma in CMMR-D patients and could be a reason why this type of glioblastoma responds well to immunotherapies, including those that employ checkpoint inhibitors., Observation: We describe a case of an adolescent with CMMR-D that had been genetically proven by whole exome sequencing (c.2T&gt;A/p.M1K and c.2521delT/p.W841fs PMS2 gene mutation). The patient presented successively with colon cancer and glioblastoma with a high mutational burden. The individualized glioblastoma therapy was based on the biological tumor profile and included immunotherapy with a combination of vaccination with autologous dendritic cells producing IL-12 and nivolumab, in addition to radiotherapy with metronomic temozolomide. The patient is still alive 21 months after the initial glioblastoma diagnosis and shows a complete therapeutic response documented by repeated magnetic resonance examinations., Conclusion: Individuals with CMMR-D should be regularly examined using established algorithms. Whole body magnetic resonance imaging can play a key role, because it enables the early diagnosis of malignancy during the asymptomatic period. Malignancies in CMMR-D patients usually exhibit a hypermutated genotype and respond to immunotherapy. Conventional glioblastoma therapy is only palliative. Patients can benefit from an individualized therapeutic plan based on the tumor biological profile. Extensive molecular analysis of the tumor tissue is necessary. Key words hereditary cancer predisposition syndromes - glioblastoma - whole exome sequencing - immunotherapy - vaccines - checkpoint inhibitors This study was supported by the research project of the Czech Ministry of Health AZV 16-33209A (Next generation sequencing and express profiling as diagnostic tools for personalized therapeutic plans in children with solid tumors). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 26. 9. 2018 Accepted: 18. 11. 2018.