Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-positive versus HPV-negative head and neck squamous cell carcinoma.

Abstract:

Background: Persistent human papillomavirus (HPV) infection is the most important etiologic agent of the oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than HPV-negative patients. However, little is known about the possible causes of the difference in the clinical outcome. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. 

Methods: We studied the intratumoral immune cell infiltrates in 51 fresh HNSCC samples collected during the primary surgery. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen presenting cells, naïve and effector T cells, Th1/Th2/Th17 lymphocytes, regulatory T cells and cytokine and chemokine levels in the tumor tissue. 

Results: There was a profound difference in the extent and characteristics of the intratumoral immune cell infiltrates in HNSCC patients depending on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher levels of infiltrating IFNγ+ CD8+ T lymphocytes, IL-17+ CD8+ T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV positive tumors had significantly lower infiltration by exhausted CD8+ T lymphocytes characterized by high PD-1 and Tim-3 expression. 

Conclusions:The presence of strong 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. Additionally, characterization of the HNSCC immune profile may represent a valuable prognostic tool in addition to the HPV status and may help to identify novel targets for therapeutic strategies, including cancer immunotherapy.

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Citation:
J Clin Oncol 32:5s, 2014 (suppl; abstr 6010)