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Cancer immunotherapy

Units : Immunobiology | ULB139

Description :

There is increasing evidence that the effect of chemotherapy on tumor growth is not cell autonomous but relies on the immune
system. The objective of our study is to better understand how the host immune system is involved in the success of chemotherapy. We
use the P815 mastocytoma of DBA/2 mice, as this tumor is poorly immunogenic, expresses well defined antigens and can elicit the
differentiation of T cells specific to tumor-associated and/or tumor-specific antigens in some conditions. We have shown recently that
treatment of DBA/2 mice bearing P815 mastocytoma with cyclophosphamide induced rejection and long-term protection in a CD4- and
CD8-dependent manner. A population of inflammatory-type dendritic cells was dramatically expanded in the lymph nodes of mice that
rejected the tumor and correlated with CD4-dependent infiltration, in tumor bed, of tumor-specific CD8+ T lymphocytes. Our data
point to a major role of CD4+ T cells in inducing chemokine expression in the tumor, provoking migration of tumor-specific CXCR3+
CD8+ T lymphocytes.Importantly, the analysis of CD8+ T cells specific to P1A/H-2Ld and P1E/H-2Kd revealed that cyclophosphamide
altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen. This question is of major
importance for immunotherapy to define the role of tumor-associated (encoded by cancer-germline gene) versus tumor-specific (encoded
by a mutated gene) antigens as tumor rejection antigens.Collectively our observation reinforce the concept that chemotherapy
relies on the immune response to achieve full remission in an experimental tumor model and suggest that that in some instances,
chemotherapy may achieve long term effects by favoring the establishment of an immune, memory-like anti-tumor response. Future
experiments will attempts to better understand the mechanism whereby chemotherapeutic agents such as cyclophosphamide allow the
establishment of an effective immune response to tumor antigens. 

List of lessors :

  • F.R.S.-FNRS et Fonds associés (hors FRIA)

  • FRIA

  • Télévie

  • Fonds associés (toutes subventions, y compris la Loterie Nat.)

  • Télévie (personnel sous convention)

  • PAI

  • Fonds spéciaux de recherche

  • Actions concertées

  • Région wallonne

  • Feder

  • Entreprises privées

  • Financement de base institutionnel