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    Kinetic analysis of immune responses associated with tumor regression

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    Group leaders : Nadège Bercovici and Alain Trautmann

    Contact: – Tel : +33(0)1 40 51 65 64

     

    Objective

    Is it possible to design immune responses able to trigger tumor regression?
    Despite recognition of tumor cells by the immune system, human solid tumors show rarely spontaneous regressions. The analysis of the relations between tumors and the human immune system are most often performed in patients with growing tumors, i.e., when the immune system is in check. We have decided to analyze in detail situations where the immune system may be stimulated in such a way that it triggers tumor regression, a study that must be performed in mice.

     

    The group

    In 2015, the group included Maxime Thoreau (PhD student, University Paris Descartes), Julia Weiss (post-doc, financed by AICR/WWCR),  Fabienne Régnier (Assistant-Ingénieur INSERM) Alain Trautmann (DRCE émérite, CNRS) et Nadège Bercovici (CR1 CNRS).

     

    Research Interests

    Recent clinical trials have demonstrated that a type of immune cell called T lymphocytes may play an important role in inducing the regression of different cancers, in particular of blood cancers. Other immune cells called macrophages accumulate in solid tumors and are numerous in growing tumors of poor prognosis. Based on these results, many people consider that, for cancer patients, lymphocytes are "good guys" and macrophages are "bad guys". However, the reality is likely to be not that Manichean. Indeed, immune responses that are efficient against infection require efficient cooperations between different cell types. We have designed a local treatment for tumor-bearing mice which has been conceived on the model of an anti-infectious response, as if there was an infection at the level of the tumor. This resulted in a systematic tumor regression.

    We perform an accurate kinetic analysis of the immune response by combining immunofluorescence in tumor sections with a global analysis of the different components of efficient immune responses. In a first tumor model, we have been able to show that the efficiency of the induced immune response rests on cooperation between macrophages and lymphocytes.

    Conceptually, for future clinical trials, it seems important to focus not only on a well-identified unique cellular actor that is maximally stimulated, but rather to take into account the cellular cooperations that have shown to be efficient in natural, anti-infectious immune responses.

    Other tumor models and modes of immune intervention will be used. The ultimate goal is to provide solid mechanistic data on key checkpoints that control tumor regression for the design of new immunotherapeutic combinations.

     

    Publications

    • Thoreau M, Penny HL, Tan K, Regnier F, Weiss JM, Lee B, Johannes L, Dransart E, Le Bon A, Abastado JP, Tartour E, Trautmann A, Bercovici N.(2015) Vaccine-induced tumor regression requires the cooperation of macrophages and T cells.Oncotarget. 6:27832-46
    • Bercovici, N. and Trautmann, A. (2012) Revisiting the role of T cells in tumor regression. Oncoimmunology 1: 346-350.
    • Wang, S. F., Fouquet, S., Chapon, M., (…)Trautmann, A., Bercovici, N. (2011) Early T cell signalling is reversibly altered in PD-1 T lymphocytes infiltrating human tumors PLoS One 6:e17621.
    • Chapon, M., Randriamampita, C., (…) Trautmann, A., Avril, M. F., Bercovici, N. (2011) Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes. J Invest Dermatol 131:1300-7.

     

    Financial support

    This project is supported by INSERM, CNRS, la Ligue Contre le Cancer (Equipe Labellisée Ligue Contre le Cancer), WORLDWIDE CANCER RESEARCH (formerly AICR).

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