CD4+ T-Cell Help in the Tumor Milieu Is Required for Recruitment and Cytolytic Function of CD8+ T Lymphocytes

Abstract

CD4 help for CD8⁺ T lymphocytes prevents tolerance and promotes the survival of effector and memory CD8⁺ T cells. Here, we describe additional helper functions that require CD4⁺ T cells within the tumor environment. CD8⁺ T-cell recruitment, proliferation, and effector function within the tumor were greatly enhanced by tumor-specific CD4⁺ T cells. Recruitment of CD8⁺ T cells was accelerated by IFN-γ–dependent production of chemokines. Production of interleukin-2 by tumor resident CD4⁺ T cells enhanced CD8⁺ T-cell proliferation and upregulated expression of granzyme B. These results highlight a novel role for tumor-specific CD4⁺ T cells in promoting CD8⁺ T-cell recruitment and cytolytic function, two previously unappreciated aspects of tumor-specific CD4 help. Cancer Res; 70(21); 8368–77. ©2010 AACR.