Abstract
Immune checkpoint inhibitor (ICI) therapies have become the most important medical therapies in many malignancies, such as melanoma, non-small-cell lung cancer, and urogenital cancers. However, due to generally low response rates of PD-(L)1 monotherapy, both PD-(L)1 combination therapies and novel therapeutics are under large-scale clinical evaluation. Thus far, clinical trials have rather suboptimally defined the patient population most likely to benefit from ICI therapy, and there is an unmet need for negative predictive markers aiming to reduce the number of non-responding patients in clinical practice. Furthermore, there is a strong need for basic tumor immunology research and innovative clinical trials to fully unleash the potential of ICI combinations for the benefit of patients.
Highlights
The basis for cancer immunotherapy was obtained in the 1940s when the observation that mainly CD8+ cytotoxic T cells, a subtype of lymphocytes, were responsible for mediating the rejection and led to the identification of the mechanistic basis of antigen-recognition by human tumor-reactive T cells
Anti-PD-(L)1 antibodies have been approved for numerous metastatic cancers and recently in adjuvant settings after operation of stage III melanoma or chemoirradation of stage III non-small-cell lung cancer (NSCLC) [2,5,6,7,8,9,10,11,12,13,14,15,16]
Pre-existing CD8+ tumor-infiltrating lymphocytes (TILs) localized in the invasive tumor margin were predictive of melanoma response to PD-1 or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor therapy [57,58,59], whereas programmed death ligand-1 (PD-L1)+ melanocytes located next to TILs was shown to lead to the secretion of interferon-gamma as a form of adaptive immune resistance [60]
Summary
The basis for cancer immunotherapy was obtained in the 1940s when the observation that mainly CD8+ cytotoxic T cells, a subtype of lymphocytes, were responsible for mediating the rejection and led to the identification of the mechanistic basis of antigen-recognition by human tumor-reactive T cells. Immune checkpoint inhibitor (ICI) therapies have become the most important medical therapies in many malignancies such as melanoma, non-small-cell lung cancer, and urogenital cancers [2,3,4,5,6,7,8,9,10,11]. Anti-PD-(L) antibodies have been approved for numerous metastatic cancers and recently in adjuvant settings after operation of stage III melanoma or chemoirradation of stage III non-small-cell lung cancer (NSCLC) [2,5,6,7,8,9,10,11,12,13,14,15,16]. We focus on the current clinical concepts and future perspectives of anti-PD-(L) therapies in cancer care
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
