The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC). We employed multiplex immunohistochemistry and immunofluorescence to evaluate the density and spatial distribution of immune cells in retrospective cohorts of OPSCC and CESC patients. This approach was complemented by transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed high densities of immune cells in both tumor stroma and tumor epithelium, whereas CESC samples were mainly characterized by the lack of immune cells in the tumor epithelium. However, in contrast to other immune cell populations, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were abundant in both segments of CESC samples and CESC-derived tumor cells expressed markedly higher levels of the PMN-MDSC chemoattractants CXCL1, CXCL5, and CXCL6 than OPSCC tumor cells. Taken together, despite their having the same etiologic agent, the immune infiltration pattern significantly differs between OPSCC and CESC, with a noticeable shift toward prominent MDSC infiltration in the latter. Our data thus present a rationale for a diverse approach to targeted therapy in patients with HPV-associated tumors of different tissue origins.

Department of Obstetrics and Gynecology 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Obstetrics and Gynecology Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Czech Republic

Department of Oncology and Radiotherapy Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Czech Republic

Department of Otorhinolaryngology and Head and Neck Surgery 1st Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Otorhinolaryngology and Head and Neck Surgery Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

SOTIO Českomoravská 2532 19b Prague 9 Prague CZ 19000 Czech Republic

The Fingerland Department of Pathology Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Czech Republic

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