Insight into Cancer Immunity: MHCs, Immune Cells and Commensal Microbiota

Abstract

Cancer cells circumvent immune surveillance via diverse strategies. In accordance, a large number of complex studies of the immune system focusing on tumor cell recognition have revealed new insights and strategies developed, largely through major histocompatibility complexes (MHCs). As one of them, tumor-specific MHC-II expression (tsMHC-II) can facilitate immune surveillance to detect tumor antigens, and thereby has been used in immunotherapy, including superior cancer prognosis, clinical sensitivity to immune checkpoint inhibition (ICI) therapy and tumor-bearing rejection in mice. NK cells play a unique role in enhancing innate immune responses, accounting for part of the response including immunosurveillance and immunoregulation. NK cells are also capable of initiating the response of the adaptive immune system to cancer immunotherapy independent of cytotoxic T cells, clearly demonstrating a link between NK cell function and the efficacy of cancer immunotherapies. Eosinophils were shown to feature pleiotropic activities against a variety of solid tumor types, including direct interactions with tumor cells, and accessorily affect immunotherapeutic response through intricating cross-talk with lymphocytes. Additionally, microbial sequencing and reconstitution revealed that commensal microbiota might be involved in the modulation of cancer progression, including positive and negative regulatory bacteria. They may play functional roles in not only mucosal modulation, but also systemic immune responses. Here, we present a panorama of the cancer immune network mediated by MHCI/II molecules, immune cells and commensal microbiota and a discussion of prospective relevant intervening mechanisms involved in cancer immunotherapies.