Cancers induced by human papillomaviruses should, in principle, be responsive to immunotherapy by virtue of expressing the immunogenic oncoproteins E6/E7 that drive malignancy. Rather, advanced forms of cervical cancer are poorly responsive to immune response-enhancing treatments involving therapeutic vaccination against these viral neo-antigens. Leveraging a transgenic mouse model for HPV-derived cancers, termed K14HPV16/H2b, we demonstrate that therapeutic vaccination with a nanoparticle-based vaccine alone or in combination with anti-PD-1/anti-CTLA4 does not elicit tumor regression nor increase the minimal CD8+ T cell infiltrates in the tumor microenvironment (TME), suggesting the presence of immunosuppressive barriers. We demonstrated that myeloid cells in lymphoid organs of K14HPV16/H2b mice possess potent immunosuppressive activity for both antigen presenting cells and CD8+ T cells that dampens the anti-tumor immune responsiveness. Our data highlight a link between HPV-induced cancers, systemic amplification of myeloid cells, and the detrimental effects of these cells on the generation of anti-tumor immune responses in the periphery, resulting in poor CD8 T cell activation and limited migration to the tumor site. SOURCE: Nadine Zangger (nadine.zangger@isb-sib.ch) - Delorenzi Swiss Institute of Bioinformatics

Pluto Bioinformatics

GSE126913: Gene expression profiling of neutrophils derived from K14HPV16/H2b and FVBN/H2b mice.