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Simple Summary: The following paper was developed as a reference for healthcare workers who are looking for information on advanced non-small cell lung cancers that lack driver mutations and their treatment with immunotherapy. The aim of the present study is to provide a reliable data source based on a review of the most current papers on the PD-1/PD-L1 and CTLA-4 inhibitors, as well as their use in medical practice. From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer has remained the leading cause of death among gynecologic malignancies. The current standard of treatment, in most cases, is a combination of surgery and chemotherapy, based on platinum agents and taxanes. Despite the increasing usage of newer drug groups, such as bevacizumab and PARP inhibitors, and the expansion of patient groups for these drugs, ovarian cancer is characterized by recurrences, particularly in the form of peritoneal implants. This review focuses on immunotherapy for ovarian cancer. It considers the current state of knowledge in areas such as cancer vaccines, adoptive cell therapy, CAR-T therapy, and anti-CTLA-4 monotherapy. The paper specifically considers PD-1/PDL-1 as drug targets. Anti-PD-1/PD-L1 monotherapy, and anti-PD-1/PD-L1 immunotherapy in combination with other agents, are analyzed. Ovarian cancer is one of the most fatal cancers in women worldwide. Cytoreductive surgery combined with platinum-based chemotherapy has been the current first-line treatment standard. Nevertheless, ovarian cancer appears to have a high recurrence rate and mortality. Immunological processes play a significant role in tumorigenesis. The production of ligands for checkpoint receptors can be a very effective, and undesirable, immunosuppressive mechanism for cancers. The CTLA-4 protein, as well as the PD-1 receptor and its PD-L1 ligand, are among the better-known components of the control points. The aim of this paper was to review current research on immunotherapy in the treatment of ovarian cancer. The authors specifically considered immune checkpoints molecules such as PD-1/PDL-1 as targets for immunotherapy. We found that immune checkpoint-inhibitor therapy does not have an improved prognosis in ovarian cancer; although early trials showed that a combination of anti-PD-1/PD-L1 therapy with targeted therapy might have the potential to improve responses and outcomes in selected patients. However, we must wait for the final results of the trials. It seems important to identify a group of patients who could benefit significantly from treatment with immune checkpoints inhibitors. However, despite numerous trials, ICIs have not become part of routine clinical practice for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials. Objectives: The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer. Method: We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China. Results: Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4+ T cell count and plasma HIV RNA remained stable throughout the treatment. Conclusions: When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4+ T cell count. [ABSTRACT FROM AUTHOR]

Simple Summary: Combination of radiotherapy and immunotherapy to antagonize tumors is one of hotspot issues currently. Immunotherapy can effectively alleviate the non-lasting effect of radiotherapy and tumor recurrence. Local radiotherapy can mobilize immune cells into tumor microenvironment and make tumors unable to escape from immune supervision. Therefore, the radio-immunotherapy achieves better curative effects on cancer patients. We have reviewed the regulation of multiple immune cells with different functions by radiotherapy, as well as the mechanism research and clinical outcomes combined with immune checkpoint inhibitors for cancer treatment, which provides new insights in the treatment strategies for certain types of cancer patients in clinic. Radiotherapy (RT) is a conventional method for clinical treatment of local tumors, which can induce tumor-specific immune response and cause the shrinkage of primary tumor and distal metastases via mediating tumor infiltration of CD8+ T cells. Ionizing radiation (IR) induced tumor regression outside the radiation field is termed as abscopal effect. However, due to the mobilization of immunosuppressive signals by IR, the activated CD8+T cells are not sufficient to maintain a long-term positive feedback to make the tumors regress completely. Eventually, the "hot" tumors gradually turn to "cold". With the advent of emerging immunotherapy, the combination of immune checkpoint blockade (ICB) and local RT has produced welcome changes in stubborn metastases, especially anti-PD-1/PD-L1 and anti-CTLA-4 which have been approved in clinical cancer treatment. However, the detailed mechanism of the abscopal effect induced by combined therapy is still unclear. Therefore, how to formulate a therapeutic schedule to maximize the efficacy should be took into consideration according to specific circumstance. This paper reviewed the recent research progresses in immunomodulatory effects of local radiotherapy on the tumor microenvironment, as well as the unique advantage for abscopal effect when combined with ICB, with a view to exploring the potential application value of radioimmunotherapy in clinic. [ABSTRACT FROM AUTHOR]

Objective: We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setting. Methods: We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1, 2016 and August 1, 2020. We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics, blood count parameters, and biochemical indicators during treatment. Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values. Kaplan--Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS). Results: A lower relative lymphocyte count (cutoff = 28.5%), higher albumin level (cutoff = 39.05 g/L), and higher absolute eosinophil count (AEC) (cutoff = 0.175 x 109/L) were significantly associated with the occurrence of irAEs, among which a higher AEC (cutoff = 0.205 x 109/L) was strongly associated with skin-related irAEs [odds ratios (ORs) = 0.163, P = 0.004]. Moreover, a higher lactate dehydrogenase level (cutoff = 237.5 U/L) was an independent predictor of irAEs of grade ≥ 3 (OR = 0.083, P = 0.023). In immune cell subgroup analysis, a lower absolute count of CD8+CD28- suppressor T cells (OR = 0.806; 95% confidence interval: 0.643--1.011; P = 0.062), which are regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant. Furthermore, a higher percentage of CD19+ B cells was associated with the occurrence of irAEs of grade ≥ 3 (P = 0.02) and grade ≥ 2 (P = 0.051). In addition, patients with any grade of irAE had a significantly high PFS (8.37 vs. 3.77 months, hazard ratios (HR) = 2.02, P = 0.0038) and OS (24.77 vs. 13.83 months, HR = 1.84; P = 0.024). Conclusions: This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors represent a promising treatment choice in many kind of tumours, including hepatocellular carcinoma (HCC). In this review, we provide an overview of the role of these new agents in the management of HCC according to the Barcelona staging system, alongside with a critical evaluation of the current status and future directions. Several clinical trials are focusing on the use of immunotherapy in HCC, alone or in combinations with antiangiogenetic agents as well as local treatment. However, the majority of those trials are still ongoing and, until now, only a few combinations were approved in the clinical practice from the regulatory authorities. Additionally, decisions about the choice of the right sequence of treatments in HCC patients in the light of the "continuum of care" principles, is still hard. In fact, it requires careful consideration in a multidisciplinary context in order to ensure a tailored treatment for each patient. Immune checkpoint inhibitors (ICIs) represent a promising treatment for many kinds of cancers, including hepatocellular carcinoma (HCC). The rationale for using ICIs in HCC is based on the immunogenic background of hepatitis and cirrhosis and on the observation of high programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes in this cancer. Promising data from phase I/II studies in advanced HCC, showing durable objective response rates (~20% in first- and second-line settings) and good safety profile, have led to phase III studies with ICIs as single agents or in combination therapy, both in first and second line setting. While the activity of immunotherapy agents as single agents seems to be limited to an "ill-defined" small subset of patients, the combination of the anti PD-L1 atezolizumab and anti-vascular endothelial growth factor bevacizumab revealed a benefit in the outcomes when compared to sorafenib in the first line. In addition, the activity and efficacy of the combinations between anti-PD-1/anti-PD-L1 antibody and other ICIs, tyrosine kinase inhibitors, or surgical and locoregional therapies, has also been investigated in clinical trials. In this review, we provide an overview of the role of ICIs in the management of HCC with a critical evaluation of the current status and future directions. [ABSTRACT FROM AUTHOR]