To Help or To Harm: Dynamic Roles of CD4⁺ T Helper Cells in Solid Tumor Microenvironments

In addition to their functional relevance in pathogenic infection and autoimmune disease, leukocytes also play critical roles in regulating cancer progression, and immunotherapies designed to enhance antitumor immune responses are becoming mainstays in clinical oncology. Complex interactions between different leukocyte subtypes recruited to neoplastic microenvironments can result in either tumor promotional or tumor suppressive programming. Therefore, understanding the mechanisms regulating the balance between these states is critical for developing improved immune-based cancer therapeutics. Effector and memory CD8⁺ T cells are well established as key mediators of tumor cytotoxicity, but the roles of CD4⁺ T cells in tumor microenvironments have not been as extensively explored. In this chapter, we review current understandings of the diverse roles played by CD4⁺ T helper cell subsets in either promoting or suppressing progression of solid tumors.