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 of 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.

Multiparametric immune profiling in HPV– oral squamous cell cancer

“…Expression of β 2 -microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome. We found that, consistent with previous reports, high numbers of CD8 + T cells at the invasive margin correlated significantly with prolonged overall survival (OS), while the number of increased T and B cell infiltrates, higher levels of IFN-γ secretion, and increased numbers of FoxP3 + T cells, all features of antiviral responses that may translate into enhanced antitumor immune responses (22)(23)(24)(25)(26), distinguishing HPV + and HPV -tumors is essential (17,27). Immune surveillance is mediated by the composition of the tumor microenvironment (TME); it is affected by a multitude of strategies tumors use to escape immune recognition.…”

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

“…Some reports have shown a decrease of tumor-infiltrating lymphocytes (TIL) in HNSCC, 9 but the clinical outcome seems to depend more on the type of TIL rather than on their total number. For instance, cytotoxic CD8 C T cells are significantly decreased in HNSCC patients if compared with healthy controls, [9][10][11][12][13][14][15] probably due to an increase apoptotic rate among this cell population in HNSCC. 13 On the top of that T cells isolated from HNSCC patients are significantly less responsive to in vitro stimulation than those isolated from healthy controls.…”

CTLA4 blockade reduces immature myeloid cells in head and neck squamous cell carcinoma

“…28 A recent study indicated that different patterns of intratumor immune cell infiltrates in HPVC HNSCC compared with HPV¡ HNSCC. 29 Interestingly, we found that CD8 C / CTLA4 remained correlated with the immunosuppressive cell population in HPV¡ HNSCC.…”