Role of Type I and II Interferons in Colorectal Cancer and Melanoma

Abstract

Cancer can be considered an aberrant organ with a hierarchical composition of different cell populations. The tumor microenvironment, including the immune cells and related cytokines, is crucial during all the steps of tumor development. In particular, type I and II interferons (IFNs) are involved in a plethora of mechanisms that regulate immune responses in cancer, thus balancing immune escape versus immune surveillance. IFNs are involved in both the direct and indirect regulation of cancer cell proliferation and metastatic potential. The mutational background of genes involved in IFNs signaling could serve as a prognostic biomarker and a powerful tool to screen cancer patients eligible for checkpoint blocking therapies. We herewith describe the latest findings regarding the contribution of IFNs in colorectal cancer and melanoma by researching their dual role as either tumor promoter or suppressor, in diverse tumor types, and microenvironmental context. We are reporting the most innovative and promising approaches of IFN-based therapies that have achieved considerable outcomes in clinical oncology practice and explain the possible mechanisms responsible for their failure.

RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition

“…This hypothesis stems from the known role of the type I IFN response in mobilizing the body's natural immunity against tumors. Recombinant IFNs were shown to improve cancer therapy due to their ability to make the tumors “hot,” i.e., more responsive to immunotherapies . The RNA fibers with controlled immunostimulation may serve as a source of natural IFN response produced by the body's own cells, as opposed to the recombinant IFNs delivered from external sources and associated with systemic toxicity .…”

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

“…Given the importance of cytokines, especially IFNs in controlling cancer, one might expect that interfering with JAKs and STATs might also have a deleterious effect. [126][127][128][129][130] However, IFNs clearly represent a double-edged sword in cancer and induce expression of inhibitory receptors and thus contribute to the "exhausted" phenotype of lymphocytes. [131][132][133] The success of checkpoint blockade inhibitors in treating cancer clearly establishes the importance of interfering with inhibitory receptors; but equally, cancers escape this therapeutic strategy by mutating JAKs.…”

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

“…Stromal cells and platelets contribute to PMN formation by secretion of pro‐angiogenic and ECM‐remodeling factors, for example, the platelet ADP receptor P2Y12. P2Y12 recruits BMDC and increases extracellular fibronectin deposition in the lung PMN, thereby selectively promoting pulmonary metastasis …”