Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma.
January 30, 2015
Source: Oncoimmunology. 2015 Jan 30;4(1):e965570. eCollection 2015.
Authors: S. Partlová, J. Bouček, K. Kloudová, E Lukešová, M. Zábrodský, M. Grega, J. Fučíková, I. Truxová, R. Tachezy, R. Špíšek, A. Fialová
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 of Cox-2 mRNA 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.
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