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

Gwendoline Rahir, Nathalie Wathelet, Aurelie Hanoteau, Coralie Henin, Guillaume Oldenhove, Adrien Galuppo, Hanane Lanaya, Didier Colau, Charles R Mackay, Benoit J Van den Eynde, Muriel Moser

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    Abstract

    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-2L(d) and P1E/H-2K(d) revealed that cyclophosphamide altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen.
    Original languageEnglish
    Pages (from-to)2841 - 2852
    Number of pages12
    JournalInternational Journal of Cancer
    Volume134
    Issue number12
    DOIs
    Publication statusPublished - 2014

    Cite this

    Rahir, Gwendoline ; Wathelet, Nathalie ; Hanoteau, Aurelie ; Henin, Coralie ; Oldenhove, Guillaume ; Galuppo, Adrien ; Lanaya, Hanane ; Colau, Didier ; Mackay, Charles R ; Van den Eynde, Benoit J ; Moser, Muriel. / Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2K(d) -specific CD8+ T cells. In: International Journal of Cancer. 2014 ; Vol. 134, No. 12. pp. 2841 - 2852.
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    title = "Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2K(d) -specific CD8+ T cells",
    abstract = "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-2L(d) and P1E/H-2K(d) revealed that cyclophosphamide altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen.",
    author = "Gwendoline Rahir and Nathalie Wathelet and Aurelie Hanoteau and Coralie Henin and Guillaume Oldenhove and Adrien Galuppo and Hanane Lanaya and Didier Colau and Mackay, {Charles R} and {Van den Eynde}, {Benoit J} and Muriel Moser",
    year = "2014",
    doi = "10.1002/ijc.28617",
    language = "English",
    volume = "134",
    pages = "2841 -- 2852",
    journal = "International Journal of Cancer",
    issn = "0020-7136",
    publisher = "Wiley-Blackwell",
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    Rahir, G, Wathelet, N, Hanoteau, A, Henin, C, Oldenhove, G, Galuppo, A, Lanaya, H, Colau, D, Mackay, CR, Van den Eynde, BJ & Moser, M 2014, 'Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2K(d) -specific CD8+ T cells', International Journal of Cancer, vol. 134, no. 12, pp. 2841 - 2852. https://doi.org/10.1002/ijc.28617

    Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2K(d) -specific CD8+ T cells. / Rahir, Gwendoline; Wathelet, Nathalie; Hanoteau, Aurelie; Henin, Coralie; Oldenhove, Guillaume; Galuppo, Adrien; Lanaya, Hanane; Colau, Didier; Mackay, Charles R; Van den Eynde, Benoit J; Moser, Muriel.

    In: International Journal of Cancer, Vol. 134, No. 12, 2014, p. 2841 - 2852.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2K(d) -specific CD8+ T cells

    AU - Rahir, Gwendoline

    AU - Wathelet, Nathalie

    AU - Hanoteau, Aurelie

    AU - Henin, Coralie

    AU - Oldenhove, Guillaume

    AU - Galuppo, Adrien

    AU - Lanaya, Hanane

    AU - Colau, Didier

    AU - Mackay, Charles R

    AU - Van den Eynde, Benoit J

    AU - Moser, Muriel

    PY - 2014

    Y1 - 2014

    N2 - 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-2L(d) and P1E/H-2K(d) revealed that cyclophosphamide altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen.

    AB - 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-2L(d) and P1E/H-2K(d) revealed that cyclophosphamide altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen.

    UR - http://onlinelibrary.wiley.com/doi/10.1002/ijc.28617/pdf

    U2 - 10.1002/ijc.28617

    DO - 10.1002/ijc.28617

    M3 - Article

    VL - 134

    SP - 2841

    EP - 2852

    JO - International Journal of Cancer

    JF - International Journal of Cancer

    SN - 0020-7136

    IS - 12

    ER -