Abstract
Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic approaches against cancer, including immune checkpoint blockade with an emphasis on anti-PD-L1 and anti-CTLA-4 monoclonal antibodies. We also analyze a growing list of other co-inhibitory and co-stimulatory markers and emphasize the mechanism of action of the principal pathway for each of these, as well as on drugs that either have been FDA-approved or are under clinical investigation. We further discuss recent advances in other immunotherapies, including cytokine therapy, adoptive cell transfer therapy and therapeutic vaccines. We finally discuss the modulation of gut microbiota composition and response to immunotherapy, as well as how tumor-intrinsic factors and immunological processes influence the mutational and epigenetic landscape of progressing tumors and response to immunotherapy but also how immunotherapeutic intervention influences the landscape of cancer neoepitopes and tumor immunoediting.
Highlights
During the last decade, immunotherapy has provided remarkable clinical responses to cancer patients
We have witnessed a great progress since with the launch of novel immune checkpoint inhibitors, including two anti–PD-1 mabs, Pembrolizumab and Nivolumab. Both mabs were initially approved against metastatic melanoma [67], non–small cell lung cancer (NSCLC), renal cell carcinoma (RCC) [68,69], head and neck squamous cell carcinoma (HNSCC) after platinum-based chemotherapy [70,71,72] and refractory classic Hodgkin’s lymphoma, later on, they were approved for any unresectable or metastatic solid tumor characterized by mismatch repair deficiency or microsatellite instability (MSI+) [17]
Macrophage markers include CD47/signal-regulatory protein alpha (SIRPα) and indoleamine-2,3-dioxygenase (IDO1 or INDO); and natural killer (NK) cell markers include CD94/NKG2A and the killer immunoglobulin-like receptor (KIR) family (Figure 1). Both T-cell Ig and mucin-domain containing-3 (TIM-3) and LAG-3 receptors are co-expressed on PD-1-expressing T cells, rendering them good candidates for combinatorial targeting with anti–PD-1 agents in PD-1 expressing tumors
Summary
Immunotherapy has provided remarkable clinical responses to cancer patients. This turning point has significantly increased our expectations for successfully treating the disease [1]. Successful immunotherapies against melanoma, non–small cell lung cancer (NSCLC). Renal cell cancer have led to active clinical trials [2,3,4,5,6,7,8,9,10,11,12]. A suitable selection of cancer patients, based on their genetic profile along with other non-genetic determinants, seems to be critical in order to achieve the most successful therapeutic responses. Cancers 2019, 11, 1472 genomic information that we need in order to predict a patient’s response to immunotherapies. We discuss the value of tumor neoantigens in the patients’ response to immunotherapy
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
