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Simple Summary: One-fifth of patients with advanced testicular germ cell tumors (TGCTs) develop platinum-refractory disease. Recent advances in the use of immunotherapy in solid tumors might have a potential impact on the treatment of these patients. The aim of this review is to elucidate the immune contexture of TGCTs, describe various immunotherapeutic biomarkers, and summarize the most recent studies of immunotherapeutic agents targeting this malignancy. In general, due to the rarity of this disease entity, a deeper understanding of its molecular landscape, combined with carefully designed biomarker-driven clinical trials, is needed in order to obtain a clearer view of the efficacy of different immunotherapeutic strategies in these patients. Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) have been investigated in epithelial ovarian cancer in first-line and recurrent settings. When used as a single agent or in combination with chemotherapy, they have largely failed to improve patients' outcome and thus, have not entered routine use in clinical practice. However, there are signs of promising activity in some early and late-phase clinical trials, combining immune checkpoint inhibitors with effective targeted agents, such as those targeting the tumor blood supply (antiangiogenics) or when taking advantage of impaired intra-cellular machinery that are unable to repair major cell damage (for example with poly-ADP-ribose inhibitors (PARP)). Further research is still needed to define predictive biomarkers that can identify patients more likely to respond to ICI combinations. New targets and treatment strategies are under investigation to define if and how immunotherapy can be incorporated into the treatment of epithelial ovarian cancer. A deep understanding of the tumor microenvironment and the recognition of tumor-infiltrating lymphocytes as a prognostic factor have resulted in major milestones in immunotherapy that have led to therapeutic advances in treating many cancers. Yet, the translation of this knowledge to clinical success for ovarian cancer remains a challenge. The efficacy of immune checkpoint inhibitors as single agents or combined with chemotherapy has been unsatisfactory, leading to the exploration of alternative combination strategies with targeted agents (e.g., poly-ADP-ribose inhibitors (PARP)and angiogenesis inhibitors) and novel immunotherapy approaches. Among the different histological subtypes, clear cell ovarian cancer has shown a higher sensitivity to immunotherapy. A deeper understanding of the mechanism of immune resistance within the context of ovarian cancer and the identification of predictive biomarkers remain central discovery benchmarks to be realized. This will be critical to successfully define the precision use of immune checkpoint inhibitors for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy, most notably immune checkpoint inhibitors (ICIs), has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. Biological markers can help to improve patient selection. However, currently available markers such as PD-1 and its ligand (PD-L1) have important limitations. For this reason, new biomarkers obtained by non-invasive methods are urgently needed. In the present review, we describe recent advances in the development of novel soluble biological markers (e.g., circulating immune cells, TMB, circulating tumor cells, circulating tumor DNA, soluble factor PD-L1, tumor necrosis factor, etc.) for patients with NSCLC treated with immunotherapy. Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (NSCLC). To date, however, only a few agents have shown promising results. Recent advances in cancer immunotherapy, most notably immune checkpoint inhibitors (ICI), have transformed the treatment scenario for these patients. Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. New biomarkers capable of reliably predicting response to ICIs are urgently needed to improve patient selection. Currently available biomarkers—including programmed death protein 1 (PD-1) and its ligand (PD-L1), and tumor mutational burden (TMB)—have major limitations. At present, no well-validated, reliable biomarkers are available. Ideally, these biomarkers would be obtained through less invasive methods such as plasma determination or liquid biopsy. In the present review, we describe recent advances in the development of novel soluble biomarkers (e.g., circulating immune cells, TMB, circulating tumor cells, circulating tumor DNA, soluble factor PD-L1, tumor necrosis factor, etc.) for patients with NSCLC treated with ICIs. We also describe the potential use of these biomarkers as prognostic indicators of treatment response and toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of advanced lung cancer is poor. Even though it can improve with immunotherapy, most patients do not respond to treatment. Identifying patients who would not benefit from therapy is an unmet goal. We hypothesized that one of the molecules present in human serum (namely, the soluble form of the unit α of the interleukin-2 receptor, sCD25) could be used as a predictor of successful immunotherapy in patients with lung cancer. Our study showed that patients who presented high sCD25 levels before treatment (≥5.99 ng/mL) and/or about three months from the start of treatment (≥7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. Serum levels of sCD25 could easily indicate patients with lung cancer who would not achieve long-term benefits from immunotherapy. Therefore, other more effective therapies could be implemented. Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10–19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04–20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICI) have represented a revolution in the treatment of non-small-cell lung cancer (NSCLC). To improve these results, combined approaches are being tested. The addition of stereotactic ablative radiotherapy (SABR) to ICI seems promising. A systematic review was performed in order to assess the safety and efficacy of SABR-ICI combination. Material and Methods: MEDLINE databases from 2009 to March 3, 2019 were reviewed to obtain English language studies reporting clinical outcomes of the combination of ICI-SABR in NSCLC. 18 out of the 429 initial results fulfilled the inclusion criteria and were selected for review. Results: Eighteen articles, including six prospective studies, describing 1736 patients treated with an ICI-SABR combination fulfilled the selection criteria. The reported mean rates for local control and distant/abscopal response rates were 71% and 41%, respectively. Eleven studies reported progression-free survival and overall survival, with a mean of 4.6 and 12.4 months, respectively. Toxicity rates were consistent with the ones attributable to ICI treatment alone. Conclusions: The ICI-SABR combination has a good safety profile and achieves high rates of local control and greater chances of obtaining abscopal responses than SABR alone, with a relevant impact on PFS. More studies are needed to improve patient selection for an optimal benefit from this approach. [ABSTRACT FROM AUTHOR]