Effective T cell activation in invaded lymph nodes from breast cancer patients
Núñez Nicolas Gonzalo1, Niborski Leticia Laura1, De La Rochere Philippe1, Viel Sophie1, Loirat Delphine1, Richer Wilfrid1, Meseure Didier2, Vincent-Salomon Anne2, Sastre-Garau Xavier2, Sedlik Christine1, Amigorena Sebastian1 and Piaggio Eliane1
1 Institut Curie, PSL Research University, INSERM U932, SIRIC, Translationnal Immunotherapy Team; 2 Institut Curie, PSL Research University, INSERM U932, Département de biologie des tumeurs
Lymph node (LN) invasion by tumor cells, which can induce immune suppression by multiple mechanisms, is a critical negative prognosis factor. We compared the phenotype and function of T cells from non-invaded (NI), invaded (I) LNs, and tumor samples from luminal breast cancer patients, to understand whether tumor-invaded LNs represent or not tolerogenic sites for T cells. As expected, T cells from the corresponding primary tumors failed to proliferate and produce effector cytokines upon stimulation ex-vivo. Unexpectedly, T cells in I TDLNs showed evidence of activation and differentiation, produced high levels of IFN-γ and responded to recall antigens. From the physiopathology standpoint, our findings indicate that while the tumor represents an immunosuppressive environment for T cells, tumor invasion of draining LNs is associated with a functional local ongoing immune response. From a clinical perspective, these results let us hypothesize that patients with LN involvement could be susceptible to immune-modulation. Moreover, our findings that CD8+, CD4+, and regulatory T lymphocytes express distinct sets of targetable immunecheckpoint molecules may guide the rationalized use of selective agonistic or antagonistic antibodies directed to these molecules in view of personalized immunotherapies. Our results indicate that while the tumor represents an immunosuppressive environment for T cells, solid tumor invasion of draining lymph nodes is a critical step in the onset of both effector and regulatory immune responses, predicting that patients with LN involvement are good candidates to benefit from immunotherapies.
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