Lymph Node Invasion by Melanoma Cells Is Not Required for the Induction of Incomplete Differentiation by Tumor‐Specific CD8+ T Cells

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Abstract
Background: Lymph node invasion by cancer cells is a poor prognostic factor and is often associated with anti‐tumor CD8+ T cell dysfunction. In this study, we investigated the role of lymph node invasion by melanoma cells in the induction of incomplete differentiation by tumor antigen‐specific CD8+ T cells.Aims: We aimed to determine whether lymph node invasion by melanoma cells is required for this specific form of anti‐tumor CD8+ T cell dysfunction.Methods and Results: We assessed lymph node invasion by the B16‐F1 and D5.1G4 murine melanoma cell lines and evaluated tumor antigen‐specific CD8+ T cell responses to these melanomas in the context of tumor‐free versus tumor‐involved lymph nodes. We demonstrate that CD8+ T cells recognizing antigen from established melanomas fail to acquire effector function, regardless of whether the tumor is stable or progressive. This CD8+ T cell dysfunction arises in the context of both tumor‐involved and tumor‐free lymph nodes draining established melanomas.Conclusions: Lymph node invasion by melanoma cells is not required for the induction of incomplete CD8+ T cell differentiation. These data and their implications for strategies to enhance CD8+ T cell responses against poorly immunogenic melanomas are discussed herein.

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