Borst et al. comprehensively review how CD4+ T cells enhance the cytotoxic T lymphocyte (CTL) antitumor response. Proper CD4+ T cell help leads to clonal expansion and differentiation of CTLs into effector and memory T cells, and increases the cytotoxicity of CTLs, resulting in enhanced antitumor response. Topics reviewed include types and spatiotemporal stages of dendritic cell involvement and the intricate interplay with T cells, co-presentation of CD4+ and CD8+ epitopes, T cell costimulatory ligands (CD40L) and receptors (CD28, CD27), and cytokine (IL-12, IL-15) and chemokine (XCL1) production.
Cancer immunotherapy aims to promote the activity of cytotoxic T lymphocytes (CTLs) within a tumour, assist the priming of tumour-specific CTLs in lymphoid organs and establish efficient and durable antitumour immunity. During priming, help signals are relayed from CD4(+) T cells to CD8(+) T cells by specific dendritic cells to optimize the magnitude and quality of the CTL response. In this Review, we highlight the cellular dynamics and membrane receptors that mediate CD4(+) T cell help and the molecular mechanisms of the enhanced antitumour activity of CTLs. We outline how deficient CD4(+) T cell help reduces the response of CTLs and how maximizing CD4(+) T cell help can improve outcomes in cancer immunotherapy strategies.
Author Info: (1) Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands. j.borst@nki.nl. (2) Division of Tumour Biology and Immunology, The Netherla
Author Info: (1) Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands. j.borst@nki.nl. (2) Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands. (3) Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands. (4) Leiden University Medical Center and ISA Pharmaceuticals, Leiden, Netherlands. (5) Institute for Systems Immunology, Wurzburg, Germany.
