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Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2Kd -specific CD8+ T cells

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Rahir, Gwendoline [ULB] Wathelet, Nathalie [ULB] Hanoteau, Aurélie [ULB] Henin, Coralie [ULB] Oldenhove, Guillaume [ULB] Colau, Didier [UCL] Van den Eynde, Benoît [UCL] Moser, Muriel [ULB]

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 this study was therefore to decipher the cellular and molecular mechanisms underlying the role of innate and adaptive immunity in chemotherapy-induced tumor rejection. 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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès interdit
Publication date 2014
Language Anglais
Journal information "International Journal of Cancer" - Vol. 134, no. 12, p. 2841-2852 (January 2014)
Peer reviewed yes
Publisher JohnWiley & Sons, Inc. ((United States) Hoboken)
issn 0020-7136
e-issn 1097-0215
Publication status Accepté/Sous presse
Affiliation UCL - SSS/DDUV - Institut de Duve
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Bibliographic reference Rahir, Gwendoline ; Wathelet, Nathalie ; Hanoteau, Aurélie ; Henin, Coralie ; Oldenhove, Guillaume ; et. al. Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2Kd -specific CD8+ T cells. In: International Journal of Cancer, Vol. 134, no. 12, p. 2841-2852 (January 2014)
Permanent URL http://hdl.handle.net/2078.1/136420