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

R Bos, LA Sherman - Cancer research, 2010 - AACR
R Bos, LA Sherman
Cancer research, 2010AACR
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 …
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.
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