Articles: carcinoma-immunology.
-
The susceptibility of Merkel cell carcinoma to the host immune response has prompted a search for effective immunotherapy. CD8-positive T lymphocytes are considered key effectors of this response, but the cellular infiltrates also harbor tumor-protective agents. By developing a comprehensive morphological and immunophenotypic map of tumor-infiltrating lymphocytes (TILS) in Merkel cell carcinoma, we aimed to establish a useful template for future studies. ⋯ Our findings support (1) the link between a brisk immune response and MCPyV positivity, (2) the supremacy of CD8+ cells in effecting immunity, and (3) the incorporation of immune inhibitors within the global infiltrate. Efforts to therapeutically arm the "effectors" and disarm the "detractors" are well focused. These will likely have the greatest impact on MCPyV-positive cases.
-
Non-small-cell lung cancer (NSCLC) is globally prevalent and associated with high rates of mortality. Immune checkpoint pathways are often exploited by tumors to evade immunity-mediated destruction, and checkpoint inhibitors can reactivate tumor-related immune responses. This review considers available clinical evidence for the use of checkpoint inhibitors in the treatment of second-line advanced NSCLC. ⋯ Level 1 evidence exists to support the use of nivolumab as second-line treatment of patients with squamous advanced NSCLC, as well as in select patients with nonsquamous disease. Benefits remain unknown in patients with targetable driver mutations, and use of PD-L1 expression to guide therapy remains controversial. Results from ongoing randomized trials evaluating biomarkers and other checkpoint inhibitors will further our understanding of this rapidly evolving area of oncology.
-
Tumors commonly harbor multiple genetic alterations, some of which initiate tumorigenesis. Among these, some tumor-specific somatic mutations resulting in mutated protein have the potential to induce antitumor immune responses. To examine the relevance of the latter to immune responses in the tumor and to patient outcomes, we used datasets of whole-exome and RNA sequencing from 97 clear cell renal cell carcinoma (ccRCC) patients to identify neoepitopes predicted to be presented by each patient's autologous HLA molecules. ⋯ Therefore, immunosuppressive molecules should be considered high-priority targets for modulating immune responses in patients with ccRCC. Blockade of these molecular pathways could be combined with immunotherapies targeting neoantigens to achieve synergistic antitumor activity. Cancer Immunol Res; 4(5); 463-71. ©2016 AACR.
-
Renal cell carcinoma (RCC) is a largely chemotherapy-resistant disease that is commonly treated with molecularly targeted therapies. Evidence suggests that RCC is also an immune-responsive disease, and checkpoint inhibitors are in active development as agents for the treatment of systemic disease. ⋯ Nivolumab is the most completely characterized anti-PD-1 agent in RCC and has been shown to be efficacious as monotherapy. Currently, there are multiple ongoing clinical trials exploring the use of combination therapy with PD-1 blockade.
-
Immune checkpoint inhibition will be the first treatment breakthrough in recurrent and metastatic urothelial carcinoma since the introduction of combination chemotherapy more than 30 years ago. Monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4, programmed death receptor 1, and programmed death receptor ligand 1 are furthest along in clinical development. Specific antibodies targeting either programmed death receptor 1 or programmed death receptor ligand 1 have demonstrated significant single-agent activity with impressive safety and tolerability for heavily pretreated patients in early-phase clinical trials. In our review, we discuss the rationale for immunotherapy in urothelial cancer, completed and ongoing studies with immune checkpoint therapy, the development of molecular subtypes of urothelial carcinoma with the potential impact of immunotherapy in these new groupings, and future directions of exploration with these agents in both early- and late-stage disease.