Table 1 Impact of multiple therapeutic strategies and approaches for counter-immunoediting therapy on innate and adaptive immunity
From: Novel strategies for cancer immunotherapy: counter-immunoediting therapy
Phase | Treatment strategies | Approaches | Target/interventions | Total effect | Impact: adaptive immunity | References | Impact: innate immunity | References |
|---|---|---|---|---|---|---|---|---|
Escape phase | Normalization strategies for stromal cells | Targeting VECs and neovascularization (Suitable for stromal cell-driven type and oncogene-driven type) | Target: VEGF/VEGFR, PDCF/PDGFR, EGF/EGFR, etc | Promotes normalization of vasculature and facilitates infiltration of effector cells | Enhances the function of CD8+ T cells; promotes the infiltration of CTL and CD4+ T cells; reduces the infiltration of Treg cells | Promotes the infiltration of NK cells; prevents the dysfunction of NK cells; reduces the recruitment of TAMs; promotes the functional maturation of DCs; reduces the number of tumor-associated mast cells | ||
Targeting CAFs (Suitable for stromal cell-driven type and oncogene-driven type) | Target: Wnt2, FAP, mesothelin, TGF-β, HIF2, NetG1, etc | Enhances the function of effector cells and remodels the TME | Restores anti-tumor T-cell responses; enhances the function of CD8+ effector T cells; decreases the number of tumor-infiltrating Tregs; inhibits the formation of Treg cells | Promotes the infiltration and activation of NK cells; reduces the recruitment of M2 macrophages; increases the number of active DCs; inhibits the infiltration of mast cells | ||||
Targeting pericytes (Suitable for stromal cell-driven type and oncogene-driven type) | Target: DLK1, IL-33, IL-10, TGFβ, PD-L1, etc | Enhances the function of effector cells and remodels the TME | Enhances anti-tumour T-cell responses; promotes the activation and recruitment of CD8+ T cells; reduces the infiltration of Treg cells | Reduces the recruitment of TAMs | [340] | |||
Targeting MSCs (Suitable for stromal cell-driven type and oncogene-driven type) | Target: IDO, IL-6, IL-8, IL-10, galectin-1, PGE2, activin-A, etc | Enhances the function of effector cells and remodels the TME | Promotes the proliferation and infiltration of T cells; promotes the recognition of tumor cells by CTL; promotes the infiltration and differentiation of B cells | Enhances NK cell-mediated cytotoxicity; inhibition of M2 macrophage polarization; restores the differentiation and function of DCs; promotes the infiltration and activation of mast cells ; | ||||
Normalization strategies of immunity | Targeting inhibitory immune receptors (Suitable for immunosuppressive cell-driven type and stromal cell-driven type) | Target: PD-1, TIGIT, VISTA, LAG3, Tim-3, CTLA-4, etc | Relieves immunosuppression of effector cells and restores the function of immune cells | Promotes the infiltration of effector T cells; maintains and enhances the function of effector T cells; inhibits the infiltration of Treg cells; enhances the function of B cells | Prevents NK cell exhaustion; enhances the NK cell-mediated cytotoxicity | |||
Targeting immunosuppressive cells (Suitable for immunosuppressive cell-driven type and stromal cell-driven type) | Target: TAMs, Treg, TANs, mast cells, Breg, etc | Relieves immunosuppression mediated by immunosuppressive cells; restores and enhances the immune function of effector cells | Promotes the activation, proliferation, infiltration and function of effector T cells; inhibits the function and proliferation of Treg cells; inhibits the function of Breg cells | Promotes the activation, infiltartion, proliferation and function of NK cells; restores the phagocytic function of macrophages; inhibitis the infiltration of M2-type macrophages; promotes the transformation from M2 type to M1 type; promotes the activation of DCs; inhibits the infiltration of tumor-associated mast cells | ||||
Targeting exhausted immune cells (Suitable for exhausted T cell-driven type and stromal cell-driven type) | Target: PTPN2, LSD1, CISH, TIGIT, tumor-associated ammonia, gut microbiota, etc | Reverses the function of T cell exhaustion | Promotes the proliferation and activation of T cells; reverses the exhaustion of T cells; enhances the effector function and proliferative capacity of Tim-3+CD8+ exhausted T cells; maintains the effector T cells stemness | Promotes the activation, infiltartionn and function of NK cells; prevents NK cell exhaustion | ||||
Normalization strategies of tumor cells | Induced expression of antigens on tumor cells (Suitable for oncogene-driven type) | Interventions: chemotherapy, radiotherapy, DNMTi, EZH2i, HDACi, IAPi, etc | Enhances the recognition of tumor cells by effector cells | Promotes tumor cell recognition and killing by T cells; enhances the function of T cells; promotes the infiltration of effector T cells; reduces the numbers and function of Treg cells | Restores the function of NK cells; promotes the activation, function and maturation of DCs | |||
Targeting the inhibitory ligands (Suitable for oncogene-driven type and immunosuppressive cell-driven type) | Target: PD-L1, PD-L2, galectin-3, LSECtin, FGL1, CD155, CD112, CEACAM-1, galectin-9, HMGB1, PtdSer, FasL, CD73, CD39, etc | Relieves tumor cell-mediated immunosuppression and enhances the function of effector cells | Promotes the activation, proliferation infiltration and function of effector T cells; prevents T cell apoptosis; inhibits the activition of Treg cells; promotes the activation of B cells | Promotes cytotoxic capacity and maturation of NK cells; enhances engulfment of macrophages; promotes the transformation from M2 type to M1 type; promotes the activation of DCs; inhibits the activiation of tumor-associated mast cells | ||||
Decrease the viability of tumor cells (Suitable for oncogene-driven type and exhausted T cell-driven type) | Interventions: Targeting metabolic and epigenetic reprogramming, targeting oncogenes, targeting cell cycle-related genes, targeting apoptosis-related proteins, etc | Reduces the immune escape ability of tumor cells and restores normal immune function | Prevents T cell apoptosis and enhances effector T cell function; enhances the infiltration and reactivation of tumor-specific T cell; reduces the infiltration of CD4+ effector regulatory T cells; promotes the infiltration of B cells | Supports the NK cell-mediated cytotoxicity; promotes the infiltartion of NK cells; inhibits the activation of TAMs; inhibits the activation of mast cells | ||||
Equilibrium phase | Neoadjuvant therapy | Target: PD-1 | Promotes intratumoral and systemic adaptive immune responses | Increases the number of T-cell clones; induces T-cell activiation | Induces cDC1 activation | [371] | ||
Cancer vaccine | Target: Neoantigen, TAAs, TSAs, etc Interventions: TLR and STING agonist, CD40 agonist, Oncolytic viru, etc | Promotes systemic adaptive immune responses | Induces strong CD4+ and CD8+ T cell immune responses; promotes the antigen-specific T-cell responses; promotes the infiltration of T cells; reduces the number of intratumoral Treg cells | Augments the cytotoxic function of NK cells; promotes the transformation from M2 type to M1 type; promotes the activation and maturation of DCs | ||||
Elimination phase | Regular exercise | Interventions: Endurance exercise, aerobic exercise, exercise training, etc | Enhances the function and mobilization of NK cells in the bloodstream, maintains their ability to perform immune surveillance | Promotes the mobilization and accumulation of tumor-infiltrating IL15Rα+ CD8+ T cells; enhances the function of CD8+ T cells; increases in absolute numbers of Tregs; increases the recruitment of Treg; promotes the mobilization of immature B cells | Promotes the infiltration and activation of NK cells; reduces the number of TAMs; regulates the polarization of TAMs; preferentially mobilizes DCs; promotes the infiltration and activation of mast cells | |||
Rational nutritional intake | Interventions: Micronutrient supplements | Enhances adaptive and innate immune system responses | Promotes the maturation and proliferation of T cells; protects T cells from apoptosis; promotes the proliferation and effector fonction of B cells | Enhances NK cell cytotoxic activity and maintains its function; promotes the inflammatory of macrophages; promotes the maturation and differentiation of DCs; restores tumor-associated DC functionality; maintains the stability of mast cells | ||||
Mental health | Interventions: Psychological interventions | Mainly enhances the activity of NK cells and maintains the immune surveillance ability of NK cells | Promotes the proliferation and activition of T cells; promotes the production of antibodies | Maintains or enhances NK cell cytotoxic activity; restores the function of DCs; inhibits the function and infiltration of mast cells | ||||
Adequate sleep | Interventions: Maintains adequate sleep | Enhances the function of adaptive immunity, promotes the formation of immune memory, and maintains the function of the innate immune system. | Promotes an increase in the number of antigen-specific CD4+ T cells and the formation of immune memory; promotes the production of antibodies | Supports the activity of NK cells | [400] |