Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells

Abstract

It has become evident that tumor-induced immuno-suppressive factors in the tumor microenvironment play a major role in suppressing normal functions of effector T cells. These factors serve as hurdles that limit the therapeutic potential of cancer immunotherapies. This review focuses on illustrating the molecular mechanisms of immunosuppression in the tumor microenvironment, including evasion of T-cell recognition, interference with T-cell trafficking, metabolism, and functions, induction of resistance to T-cell killing, and apoptosis of T cells. A better understanding of these mechanisms may help in the development of strategies to enhance the effectiveness of cancer immunotherapies.

Keywords:

• immunosuppression
• immunotherapy
• immunosuppressive factors
• T cells
• tumor microenvironment

Abbreviations:

• 1MT, 1-methyltryptophan
• COX2, cyclooxygenase-2
• Gal1, galectin-1
• GM-CSF, granulocyte macrophage colony-stimulating factor
• GPI, glycosylphosphatidylinositol
• HDACi, histone deacetylase inhibitor
• HLA, human leukocyte antigen
• IDO, indoleamine-2,3- dioxygenase
• IL-10, interleukin-10
• IMC, immature myeloid cell
• iNOS, inducible nitric-oxide synthase
• MDSC, myeloid-derived suppressor cells
• MHC, major histocompatibility
• MICA, MHC class I related molecule A
• MICB, MHC class I related molecule B
• NO, nitric oxide
• PD-1, program death receptor-1
• PD-L1, programmed death ligand 1
• PGE2, prostaglandin E2
• SOCS, suppressor of cytokine signaling
• STAT3, signal transducer and activator of transcription 3
• SVV, survivin
• TCR, T-cell receptor
• TGF-β, transforming growth factor β
• TRAIL, TNF-related apoptosis-inducing ligand
• PARP, poly ADP-ribose polymerase
• RCAS1, receptor-binding cancer antigen expressed on Siso cells 1
• RCC, renal cell carcinoma
• VCAM-1, vascular cell adhesion molecule-1
• XIAP, X-linked inhibitor of apoptosis protein

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Benjamin Yang for his helpful comments and critical review of the manuscript. This review is not intended to be an encyclopedic one, and we apologize to those whose work is not cited.