title: Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma.
abstract: Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ+CD8+T lymphocytes, IL-17+CD8+T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression ofCox-2mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.
authors.affiliation: Sotio, Prague , Czech Republic ; Department of Immunology; 2nd Faculty of Medicine; Charles University; Motol University Hospital ; Prague, Czech Republic.
authors.forename: Simona
authors.initials: S
authors.lastname: Partlová
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery; 1st Faculty of Medicine; Charles University and Motol University Hospital ; Prague, Czech Republic ; Institute of Microbiology ASCR ; Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Bouček
authors.affiliation: Sotio, Prague , Czech Republic ; Department of Immunology; 2nd Faculty of Medicine; Charles University; Motol University Hospital ; Prague, Czech Republic.
authors.forename: Kamila
authors.initials: K
authors.lastname: Kloudová
authors.affiliation: Department of Experimental Virology; Institute of Hematology and Blood Transfusion ; Prague, Czech Republic ; Department of Genetics and Microbiology; Faculty of Science; Charles University ; Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Lukešová
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery; 1st Faculty of Medicine; Charles University and Motol University Hospital ; Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Zábrodský
authors.affiliation: Department of Pathology and Molecular Medicine; 2nd Faculty of Medicine; Charles University and Motol University Hospital ; Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Grega
authors.affiliation: Sotio, Prague , Czech Republic ; Department of Immunology; 2nd Faculty of Medicine; Charles University; Motol University Hospital ; Prague, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Fučíková
authors.affiliation: Sotio, Prague , Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Truxová
authors.affiliation: Department of Experimental Virology; Institute of Hematology and Blood Transfusion ; Prague, Czech Republic ; Department of Genetics and Microbiology; Faculty of Science; Charles University ; Prague, Czech Republic.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tachezy
authors.affiliation: Sotio, Prague , Czech Republic ; Department of Immunology; 2nd Faculty of Medicine; Charles University; Motol University Hospital ; Prague, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Špíšek
authors.affiliation: Sotio, Prague , Czech Republic ; Department of Immunology; 2nd Faculty of Medicine; Charles University; Motol University Hospital ; Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Fialová
keywords: CD8+ T lymphocytes; Cox-2, cyclooxygenase 2; HNSCC; HNSCC, head and neck squamous cell carcinoma; HPV; HPV, human papillomavirus; PD-1; PD-1, programmed cell death 1; PD-L1, programmed cell death-ligand 1; Tim-3; Tim-3, T cell immunoglobulin and mucin protein 3; Treg, regulatory T cell; mDC, myeloid dendritic cell; pDC, plasmacytoic dendritic cell