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Lack of MHC class II molecules favors CD8 + T- cell infiltration into tumors associated with an increased control of tumor growth
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Edité par CCSD ; Taylor & Francis -
International audience. Regulatory T-cells (Tregs) are crucial for the maintenance of immune tolerance and homeostasis as well as forpreventing autoimmune diseases, but their impact on the survival of cancer patients remains controversial. Inthe TC-1 mouse model of human papillomavirus (HPV)-related carcinoma, we have previously demonstratedthat the therapeutic efficacy of the CyaA-E7-vaccine, targeting the HPV-E7 antigen, progressively declineswith tumor growth, in correlation with increased intratumoral recruitment of Tregs. In the present study, wedemonstrated that these TC-1 tumor-infiltrating Tregs were highly activated, with increased expression ofimmunosuppressive molecules. Both intratumoral effector CD4C T-cells (Teffs) and Tregs expressed highlevels of PD-1, but anti-PD-1 antibody treatment did not impact the growth of the TC-1 tumor nor restorethe therapeutic effect of the CyaA-E7 vaccine. To analyze the mechanisms by which Tregs are recruited tothe tumor site, we used MHC-II KO mice with drastically reduced numbers of CD4C effector T-cells. Wedemonstrated that these mice still had significant numbers of Tregs in their lymphoid organs which wererecruited to the tumor. In MHC-II KO mice, the growth of the TC-1 tumor was delayed in correlation with astrong increase in the intratumoral recruitment of CD8C T-cells. In addition, in mice that spontaneouslyrejected their tumors, the infiltration of E7-specific CD8C T-cells was significantly higher than in MHC-II KOmice with a growing tumor. These results demonstrate that tumor-specific CD8C T-cells can be efficientlyactivated and recruited in the absence of MHC class II molecules and of CD4C T-cell help.
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