Table 1.
Pro-tumourigenic and anti-tumourigenic functions of immune cells*.
| Immune cell | Tumor promotion | Tumor suppression | Cancer type | References |
|---|---|---|---|---|
| B cells | •Secretes cytokines (IL-10, TGF-β, lymphotoxin), immunosuppressive molecules (PD-L1, granzyme B) •Inhibit T-cell activation and CD4+ T cell response •Promote metastasis and angiogenesis •Suppress CD8+ T cell and NK cell anti-tumor activity •Recruit myeloid cells antibodies to induce immunosuppressive environment |
•Promotes CD4+ and CD8+ activity •Prolongs T cell survival •Secrete cytokine (IFNγ) and IgG •Recruit NK cells to eradicate cancer cells •Enhance antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells and phagocytosis in macrophages •Act as antigen presenting cells to stimulate anti-tumor response |
•Bladder •Breast •Cervical •Colorectal •Diffuse large B-cell lymphoma •Gastric •Glioblastoma •Head and neck •Immunoblastic sarcoma •Leukemia •Liver •Lung •Melanoma •Myeloma •Non-Hodgkin lymphoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma •Thyroid |
(7–9) |
| CD4+ Th1 cells | •Promotes CTLs survival and activity •Recruit and activate antigen-presenting cells, NK cells, and M1 •cell infiltration •Secretes cytokines (IFNγ, TNF-α, IL-2) to Inhibit angiogenesis and induce cancer cell apoptosis |
•Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Leukemia •Liver •Lung •Melanoma •Myeloma •Non-Hodgkin lymphoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma |
(10–14) | |
| CD4+ Th17 cells | •Secrete cytokine (IL-17A) •Suppresses immune response and promotes angiogenesis •Recruits immunosuppressive |
•Activates CTLs •Secretes cytokines (IFNγ, IL-17F, IL-21) |
•Bladder •Breast •Cervical •Colorectal •Gastric •Glioblastoma •Head and neck •Leukemia •Lung •Melanoma •Non-Hodgkin lymphoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma |
(10, 13–15) |
| CD4+ Th2 cells | •Cytokine production (IL-10, IL-4, IL-5) •Inhibit CTL proliferation |
•Recruits M1 for arginase-mediated cancer eradication in adoptive cell therapy •Priming of CTLs |
•Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Leukemia •Liver •Lung •Melanoma •Myeloma •Non-Hodgkin lymphoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma |
(10, 11, 13, 14, 16) |
| CD4+ Treg cells | •Exhaustion of T-cell and NK activities •Inhibit expansion of CD4+ and CD8+ T cells •Suppresses antigen-presenting cell activities and expression of antigen-presenting molecules and inflammatory cytokines •Inhibit B cell antibody production •Strongly promotes immunosuppressive tumor environment •Induces ATP catabolism •Secretes cytokines (IL-10, TGF-β, IL-35), immunosuppressive molecules (granzyme B, perforins) |
•Regulate inflammation to restore immune response | •Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Hepatocellular carcinoma •Leukemia •Lung •Melanoma •Mesothelioma •Myeloma •Non-Hodgkin lymphoma •NSCLC •Ovarian •Pancreatic •Papillary thyroid •Prostate •Renal cell carcinoma •Squamous cell carcinoma |
(11, 17–19) |
| CD8+ cells | •Activity inhibited by immunosuppressive environment and cells | •Perforin or Fas-mediated cytotoxic response to cancer cells •Secretes cytokines (IFNγ, TNF-α) |
•B-cell non-Hodgkin lymphoma •Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Hodgkin Lymphoma •Leukemia •Liver •Lung •Lymphoma •Melanoma •Myeloma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma |
(12, 20, 21) |
| Dendritic cells | •Secretes cytokines (TGF-β, IL-10, IL-6), growth factors (VEGF), immunosuppressive molecules/enzyme (arginase, iNOS, IDO, COX2) •Reduced priming of CD8+ T cells in response to elevated levels of B-catenin •Direct suppression of CD8+ T cell activity by arginase and Stimulate Treg formation |
•Assists in priming of CD4+ and CD8+ T cells through tumor antigens •Adaptive immune response •Secretes cytokines (IL-2, IL-12, type I IFN), T-cells costimulatory molecules and cytokines for Th1 and Th17 priming (TREM-1) •Links the innate and adaptive immunity as antigen-presenting cells |
•Bladder •Blastic plasmacytoid dendritic cell neoplasm •Breast •Cervical •Colorectal •Gastric •Glioblastoma •Head and neck •Hepatocellular carcinoma •Lung •Melanoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma •Thyroid |
(11, 22–26) |
| Macrophages | •Pro-tumourigenic TAM (M2) •Secretes cytokines (TGF-β, IL-10, IL-8), growth factors (VEGF, EGF, PDGF), immunosuppressive molecules (FAP-a, HO-1), and ECM remodeling (MMP-9) •Direct immunosuppression of CD8+ T cells •Induces EMT •Enhance tumor cell migration and pre-metastatic niche •Promote angiogenesis and metastasis |
•Anti-tumourigenic (M1) •Secretes cytokines (IL-12, type I IFN) and NO •Eliminate cancer cells through phagocytosis and cytotoxicity |
•Bladder •Bone metastasis •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Leukemia •Liver •Lung •Melanoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Sarcoma •Squamous cell carcinoma •Thyroid |
(10, 11, 27–31) |
| Mast cells | •Secretes cytokine (IL-6, IL-13, CSF), growth factors (TGFβ, VEGF, FGF-2), protease (tryptase) •Promote metastasis and Enhance immunosuppressive effects of MDSC and inflammation from other immune cells |
•Recruit and activate T cells and DC •Secrete cytokines (IFNγ, TNF-α) |
•Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Diffuse large B-cell lymphoma •Gastric •Glioblastoma •Head and neck •Hepatocellular carcinoma •Leukemia •Lung •Melanoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Sarcoma •Squamous cell carcinoma •Thyroid |
(32–34) |
| MDSC | •Exhaustion of T-cell activities •Induce NK anergy •Inhibit T-cell infiltration •Induces TAM differentiation •Strongly promotes immunosuppressive tumor environment •Induces EMT •Enhance tumor cell migration and preparing the pre-metastatic niche •Secrete (M-CSF), growth factors (VEGF), immunosuppressive molecules (ROS, iNOS, ARG1) |
•Bladder •Breast •Cervical •Colorectal •Gastric •Glioblastoma •Head and neck •Hepatocellular carcinoma •Hodgkin's lymphoma •Leukemia •Lung •Melanoma •Non-Hodgkin's lymphoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Sarcoma •Squamous cell carcinoma •Thyroid |
(10, 11, 35) | |
| Neutrophils | •Pro-tumourigenic TAN (N2) in late tumourigensis •Expression of cytokines (TGFβ, CXCL8) growth factors (VEGF), (arginase, ROS), ECM remodeling (MMP-9) •Promotes angiogenesis, metastasis, cancer cell proliferation •Induce NK anergy |
•Anti-tumourigenic (N1) during early tumourigenesis •Secrete cytokines (IFNγ, TNFα) •TRAIL and FasL-mediated apoptosis of cancer cells •apoptosis of cancer cells •Antibody-dependent cell-mediated cytotoxicity (ADCC) of cancer cells •Elimination of tumor cells during early tumourigenesis activate T Cells |
•Bladder •Breast •Cervical •Cholangiocarcinoma •Chronic neutrophilic leukemia •neutrophilic leukemia •Colorectal •Gastric •Glioblastoma •Head and neck •Liver •Lung •Melanoma •Non-Hodgkin lymphoma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma •Thyroid |
(36–40) |
| NK cells | •Rapid death of NK cells through lack of IL-2 and IL-15 | •ADCC, FasL, TRAIL-mediated apoptosis of cancer cells •Secretes cytokines (IFNγ, TNFα) •Promote DC maturation and elimination of immature DC •Cross-talk between macrophages, NKT, DC, and T-cells for synergise anti-tumor response |
•Anaplastic thyroid cancer •Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Liver •Lung •Melanoma •Natural killer cell leukemia •Natural •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma •carcinoma |
(41–44) |
| NKT cells | •Secretes cytokines (IL-4, IL-13, TGFβ) •Suppress Type I NKT and CD8+ T cell anti-tumor activity |
•Type I NKT cells produces cytotoxic response to cancer cells •Recruits and activates Th1 cells •Abolish immunosuppressive functions in TAM, TAN and MDSC •Secretes cytokines (IFNγ, IL-12, IL-21) |
•Bladder •Breast •Cervical •Cholangiocarcinoma •Colorectal •Gastric •Glioblastoma •Head and neck •Liver •Lung •Melanoma •Myeloma •Natural killer/T-cell lymphomas •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma |
(45–50) |
| γδ T cells | •Secrete cytokines (IL-10, IL-17, TGFβ) and immunosuppressive molecules (PD-L1) •Inhibit DC activities and T-cell differentiation •Induce immunosenescence in DC and T-cells •Promote immunosuppression and angiogenesis •Recruitment of MDSC and |
•Perforin, TNF, TRAIL mediated cytotoxic response to cancer cells •Secretes cytokines (IFNγ, TNF-α) •Links the •Links the innate and adaptive immunity as antigen-presenting cells •Enhance antibody production through interaction with B-cells •Promote DC maturation and differentiation of naive CD4+ T cells to CTL •Improve NK cell cytotoxicity against cancer cells |
•Bladder •Breast •Cervical •Colorectal •Gastric •Glioblastoma •Head and neck •Leukemia •Lung •Lymphoma •Melanoma •Myeloma •NSCLC •Ovarian •Pancreatic •Prostate •Renal cell carcinoma •Squamous cell carcinoma |
(51–53) |
*
Immune cell can have both pro-tumourigenic and anti-tumourigenic activity based on tumor type, microenvironment, stage, localization, and immune subset.