Lack of MHC class II molecules favors CD8 + T- cell infiltration into tumors associated with an increased control of tumor growth

Nada Chaoul (1) , Alexandre Tang (1) , Belinda Desrues (1) , Marine Oberkampf (1) , Catherine Fayolle (1) , Daniel Ladant (2) , Alexander Sainz-Perez (1) , Claude Leclerc (1)

1 Régulation Immunitaire et Vaccinologie
2 Biochimie des Interactions Macromoléculaires / Biochemistry of Macromolecular Interactions

Regulatory T-cells (Tregs) are crucial for the maintenance of immune tolerance and homeostasis as well as for preventing autoimmune diseases, but their impact on the survival of cancer patients remains controversial. In the TC-1 mouse model of human papillomavirus (HPV)-related carcinoma, we have previously demonstrated that the therapeutic efficacy of the CyaA-E7-vaccine, targeting the HPV-E7 antigen, progressively declines with tumor growth, in correlation with increased intratumoral recruitment of Tregs. In the present study, we demonstrated that these TC-1 tumor-infiltrating Tregs were highly activated, with increased expression of immunosuppressive molecules. Both intratumoral effector CD4C T-cells (Teffs) and Tregs expressed high levels of PD-1, but anti-PD-1 antibody treatment did not impact the growth of the TC-1 tumor nor restore the therapeutic effect of the CyaA-E7 vaccine. To analyze the mechanisms by which Tregs are recruited to the tumor site, we used MHC-II KO mice with drastically reduced numbers of CD4C effector T-cells. We demonstrated that these mice still had significant numbers of Tregs in their lymphoid organs which were recruited to the tumor. In MHC-II KO mice, the growth of the TC-1 tumor was delayed in correlation with a strong increase in the intratumoral recruitment of CD8C T-cells. In addition, in mice that spontaneously rejected their tumors, the infiltration of E7-specific CD8C T-cells was significantly higher than in MHC-II KO mice with a growing tumor. These results demonstrate that tumor-specific CD8C T-cells can be efficiently activated and recruited in the absence of MHC class II molecules and of CD4C T-cell help.

Mots clés: CD8+ T-cells; immunosuppression; immunotherapy; regulatory T-cells; tumor microenvironment

Domaines: Sciences du Vivant [q-bio]; Cancer; Immunologie

Nada Chaoul, Alexandre Tang, Belinda Desrues, Marine Oberkampf, Catherine Fayolle, et al.. Lack of MHC class II molecules favors CD8 + T- cell infiltration into tumors associated with an increased control of tumor growth. OncoImmunology, 2017, 7 (3), pp.e1404213. ⟨10.1080/2162402X.2017.1404213⟩. ⟨pasteur-02572236⟩