Figure 1.

Select tumor functions, anti-tumor immune components, and their interactions. (a) tumor-associated and tumor-specific antigens (TAA/TSA) are processed by antigen-presenting cells (APC), which then (b) communicate with both CD4+ and CD8+ T cells (CTL) through major histocompatibility class I and II (MHC-I, MHC-II), along with co-signals CD28/B7 and CD40/CD40L. (c) a complex interplay of cytokines including interleukin-2 (IL-2), IL-12, IL-15, IFNγ, TGF-β that are released by immune cells and from the tumor microenvironment tightly control the activation of the immune system through these steps (blue arrows/text). (d) this is further influenced by an individual’s microbiome, influencing immune responses. (e) Chemokines such as CXCL12, CCL5, and others (red arrows/text) mediate recruitment of immune cells to the tumor. Meanwhile, immune regulation is achieved through cellular components such as (f) regulatory T cells (Treg), as well as (g) myeloid-derived suppressor cells (MDSC) and a balance of M1 and M2 tumor-associated macrophages (TAM) in the tumor microenvironment (TME). (h) cancer associated fibroblasts (CAF) express fibroblast associated protein (FAP) and decrease responses to immunotherapies through generation of cytokines and chemokines, as well as causing a desmoplastic reaction in the TME. (i) specific tumor mutations also can provoke pro- or anti-immune functions through various mechanisms. (j) immune evasion is further achieved through depletion of metabolites, decreased glucose, oxygen (O2), tryptophan, arginine, and glutamine. (k) based on these factors, CD8+ CTLs perform direct killing of tumor cells after activation of the T cell receptor (TCR) and a balance of costimulatory (e.g., PD-1, LAG-3) and coinhibitory (e.g., 4-1BB, OX40) signals. Created with BioRender.