Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy

• DOI: 10.1016/bs.ai.2015.12.003
• Publication Date: 2016-01-23T01:55:11Z
• Authors: Stefani Spranger; Ayelet Sivan; Leticia Corrales; Thomas F. Gajewski
• Keywords: 0301 basic medicine; Immunity, Cellular; T-Lymphocytes; Neoplasms, Experimental; Lymphocyte Activation; Gastrointestinal Microbiome; 3. Good health; Mice; 03 medical and health sciences; Treatment Outcome; Antigens, Neoplasm; Neoplasms; Tumor Microenvironment; Animals; Humans; Immunotherapy; Wnt Signaling Pathway

Despite recent clinical advances in immunotherapy, a fraction of cancer patients fails to respond to these interventions. Evidence from preclinical mouse models as well as clinical samples has provided evidence that the extent of activated T cell infiltration within the tumor microenvironment is associated with clinical response to immunotherapies including checkpoint blockade. Therefore, understanding the molecular mechanisms mediating the lack of T cell infiltration into the tumor microenvironment will be instrumental for the development of new therapeutic strategies to render those patients immunotherapy responsive. Recent data have suggested that major sources of intersubject heterogeneity include differences in somatic mutations in specific oncogene pathways between cancers of individual subjects and also environmental factors including commensal microbial composition. Successful identification of such causal factors should lead to new therapeutic approaches that may facilitate T cell entry into noninflamed tumors and expand the fraction of patients capable of responding to novel immunotherapies.