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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.

Interventional oncology is a subspecialty field of interventional radiology that addresses the diagnosis and treatment of cancer and cancer-related problems by using targeted minimally invasive procedures performed with image guidance. Immuno-oncology is an innovative area of cancer research and practice that seeks to help the patient's own immune system fight cancer. Both interventional oncology and immuno-oncology can potentially play a pivotal role in cancer management plans when used alongside medical, surgical, and radiation oncology in the care of cancer patients., (© RSNA, 2019.)

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.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment., (© 2016 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

There have been major advances in the immunotherapy of cancer in recent years, including the development of T cell engagers - antibodies engineered to redirect T cells to recognize and kill cancer cells - for the treatment of haematological malignancies. However, the field still faces several challenges to develop agents that are consistently effective in a majority of patients and cancer types, such as optimizing drug dose, overcoming treatment resistance and improving efficacy in solid tumours. A new generation of T cell-targeted molecules was developed to tackle these issues that are potentially more effective and safer. In addition, agents designed to engage the antitumour activities of other immune cells, including natural killer cells and myeloid cells, are showing promise and have the potential to treat a broader range of cancers., (© 2024. Springer Nature Limited.)

Breast cancer is the most common type of cancer affecting women worldwide and its risk increases with age. Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) behaves more aggressively, with earlier relapses and poorer survival outcomes. Although the incidence of TNBC decreases with age, it still affects about 10% of older women with breast cancer. The management of TNBC in older patients is particularly challenging as chemotherapy is the main treatment choice in both early and advanced diseases and older patients are often prone to increased treatment-related toxicities. This review highlights the specific considerations in this vulnerable group of patients and summarizes the current evidence for TNBC management in older adults from early to late stage of disease. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) became a treatment option in most tumor types and improved survival in patients with cancer in the last decade. Older patients with cancer are underrepresented in the pivotal clinical trials with ICIs. Older patients with cancer often have significant comorbidities and geriatric syndromes like frailty, which can complicate cancer care and treatment decisions. Frailty is among the most prevalent geriatric syndromes in patients with cancer and could lead to inferior survival and a higher risk of complications in patients treated with chemotherapy. However, the effect of frailty on the efficacy and safety of ICIs is understudied. This review focuses on the available evidence regarding the association between frailty and ICI efficacy and safety. Although the survival benefits of ICIs have generally been shown to be independent of age, the available real-world data has generally suggested higher rates of immune-related adverse events (irAEs) and treatment discontinuation in older patients. While international organizations recommend conducting a comprehensive geriatric assessment CGA to assess and address frailty before the start of anti-cancer therapies, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher is frequently used in clinical practice as synonymous with frailty, albeit with significant limitations. The available data has generally demonstrated diminished ICI efficacy in patients with an ECOG 2 or higher compared to patients with better performance status, while the incidence of high-grade irAEs were similar. Whilst evidence regarding outcomes with ICI in older patients and in those with sub-optimal performance status is growing, there is very limited data specifically evaluating the role of frailty with ICIs. These studies found a shortened overall survival, yet no evidence of a lower response rate to ICIs. These patients experienced more AEs, but they did not necessarily have a higher incidence of irAEs. [ABSTRACT FROM AUTHOR]

Background: This study aims to identify symptom clusters in patients with intermediate and advanced liver cancer receiving targeted immunotherapy, focusing on core and bridge symptoms to establish a foundation for precise symptom management., Methods: This study used a cross-sectional survey and utilized convenience sampling from May 2023 to January 2024 at a third-class hospital in Shanghai, China. The severity of symptoms in liver cancer patients during treatment was evaluated using the Memorial Symptom Assessment Scale. Network analysis was employed to depict the interrelation of symptom clusters and identify core and bridge symptoms., Results: The symptoms were classified by severity into five clusters: oral, gastrointestinal, fatigue-related, body image, and pain-sleep. Within the symptom network, the core symptoms were pain, "I don't look like myself," and nausea, while the critical bridge symptoms included pain, itching, and feeling bloated. The strongest connections were observed between nausea and vomiting, followed by taste changes and dry mouth, as well as weight loss and "I don't look like myself.", Conclusion: In patients receiving targeted immunotherapy for intermediate and advanced liver cancer, multiple symptoms can emerge simultaneously, forming interconnected clusters. By identifying and intervening in core and bridge symptoms, personalized management strategies can be developed to relieve other symptoms and disrupt connections between symptom clusters, thereby enhancing symptom management efficacy. This study has significant clinical and research implications, offering new insights to improve patients' quality of life and treatment outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.)

Immunotherapy has revolutionized the treatment of cancer but continues to be constrained by limited response rates, acquired resistance, toxicities and high costs, which necessitates the development of new, innovative strategies. The discovery of a connection between the human microbiota and cancer dates back 4,000 years, when local infection was observed to result in tumour eradication in some individuals. However, the true oncological relevance of the intratumoural microbiota was not recognized until the turn of the twentieth century. The intratumoural microbiota can have pivotal roles in both the pathogenesis and treatment of cancer. In particular, intratumoural bacteria can either promote or inhibit cancer growth via remodelling of the tumour microenvironment. Over the past two decades, remarkable progress has been made preclinically in engineering bacteria as agents for cancer immunotherapy; some of these bacterial products have successfully reached the clinical stages of development. In this Review, we discuss the characteristics of intratumoural bacteria and their intricate interactions with the tumour microenvironment. We also describe the many strategies used to engineer bacteria for use in the treatment of cancer, summarizing contemporary data from completed and ongoing clinical trials. The work described herein highlights the potential of bacteria to transform the landscape of cancer therapy, bridging ancient wisdom with modern scientific innovation., (© 2024. Springer Nature Limited.)

This ENETS guidance paper, developed by a multidisciplinary working group, provides up‐to‐date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11–12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first‐line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second‐line treatment. Immunotherapy plays a minor role in biomarker‐unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease. [ABSTRACT FROM AUTHOR]

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e - oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO 2 ), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO - ), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO 2 - , and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO 2 - , and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer., (© 2024 Wiley-VCH GmbH.)

Lymphatic transport maintains homeostatic health and is necessary for immune surveillance, and yet lymphatic growth is often associated with solid tumour development and dissemination. Although tumour-associated lymphatic remodelling and growth were initially presumed to simply expand a passive route for regional metastasis, emerging research puts lymphatic vessels and their active transport at the interface of metastasis, tumour-associated inflammation and systemic immune surveillance. Here, we discuss active mechanisms through which lymphatic vessels shape their transport function to influence peripheral tissue immunity and the current understanding of how tumour-associated lymphatic vessels may both augment and disrupt antitumour immune surveillance. We end by looking forward to emerging areas of interest in the field of cancer immunotherapy in which lymphatic vessels and their transport function are likely key players: the formation of tertiary lymphoid structures, immune surveillance in the central nervous system, the microbiome, obesity and ageing. The lessons learnt support a working framework that defines the lymphatic system as a key determinant of both local and systemic inflammatory networks and thereby a crucial player in the response to cancer immunotherapy., (© 2024. Springer Nature Limited.)

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]

The immune system interacts with many nominal 'danger' signals, endogenous danger‐associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)‐associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti‐cancer immune and targeted therapies. Cross‐disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes. [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.

Malignant melanoma is an aggressive cancer associated with a poor prognosis in patients with metastatic disease. As in many other cancers, the incidence of melanoma rises with age; and combined with the longer life expectancy, this led to an increasing prevalence of melanoma in the older population. Recently, immune checkpoint inhibitors significantly improved the treatment of melanoma given their efficacy and tolerability profile. Two major classes of agents include the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors, such as ipilimumab, and the anti-programmed death-ligand 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab. Treatment of metastatic disease with immune checkpoint inhibitors demonstrated improved efficacy and better safety profiles compared to cytotoxic drugs and appears to be an attractive treatment option. Nevertheless, there is a need for tools designed to better predict which older patients will benefit from its use and who will experience toxicities related to the treatment. Current data do not show a major increase in toxicity rates in older patients. However, patients above 75 are often under-represented and those who are included are not representative of the general population of older patients, thereby also stressing the need for real-life data. Ongoing research is aiming at maximizing the potential treatment efficacy and developing novel immune-targeting modalities. Future studies should include older patients and assess geriatric domains in these older patients to better guide decision-making. This review discusses published clinical trials and where known, the efficacy and toxicity in older patients. Moreover, the clinical implications and future perspectives are discussed, with current recommendations for older patients, management of toxicities, and a proposal for an initial approach to the treatment of older patients with metastatic melanoma. [ABSTRACT FROM AUTHOR]

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double‐blind, placebo‐controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials. [ABSTRACT FROM AUTHOR]

The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). Prolonged survival in excess of 2 years can be expected in most patients with sensitive tumours and well-preserved liver function that renders them fit for sequential therapies. With different choices available in any given setting, the robustness of the evidence of efficacy and a correct matching of the safety profile of a given agent with patient characteristics and preferences are key in making sound therapeutic decisions. The recommendations in this document amend the previous EASL Clinical Practice Guidelines and aim to help clinicians provide the best possible care for patients today. In view of several ongoing and promising trials, further advances in systemic therapy of hepatocellular carcinoma are foreseen in the near future and these recommendations will have to be updated regularly. [ABSTRACT FROM AUTHOR]

A novel method for precise detection of allergen-specific IgE via immobilizing His-tagged allergens to paper-based device To the Editor, Allergic diseases are characterized by elevated specific IgE (sIgE) serum levels against certain allergens.1,2 Thus, the fast and precise detection of sIgE is necessary for the diagnosis of allergic diseases. The features of this strategy for allergen immobilization were highlighted with strong and specific binding site, particularly the preservation of sIgE-binding activity without covering any IgE-binding epitopes of allergens (Figure 1B). [Extracted from the article]

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.)