Impact of vitamin D and HPV on the immunecheckpoint molecule expression in head and neck squamous cell carcinoma

Introduction:

Vitamin D deficiency is frequently observed among patients with head and neck squamous cell carcinoma (HNSCC), being associated with an impaired antitumor immune activity.

Building on this, we examined to what extent vitamin D influences the immunological interplay between tumor and host immune cells by focusing on a subset of immunecheckpoint molecules.

Methods:

HNSCC tumor tissue samples from 52 patients with adequate serum levels of vitamin D and 63 patients with vitamin D deficiency, were subjected to conventional immunohistochemistry in order to analyze the tumoral expression of CD80, B7-H3, B7-H4, PD-L1, MHC1 as well as the PD-L1- and CD80-expression on intra- and peritumoral leukocytes. Additionally, the staining results were correlated with the HPV status.

Results:

An adequate vitamin D status was associated with higher tumoral levels of CD80, B7-H3 and MHC1 as well as an increased CD80 expression on peritumoral leukocytes. In contrast, vitamin D deficiency and HPV negativity correlated with an increased B7-H4 tumor expression. HPV positive tumor samples expressed PD-L1 and MHC1 to a higher degree, whereas B7-H3- expression was reduced among these patients.

Conclusions:

In summary, these observations concord to suggest that sufficient vitamin D levels improve the ratio of activating and inhibitory immunecheckpoints in the HNSCC tumor microenvironment, enhancing the effectivity of tumor specific immune responses. Further, vitamin D as well as HPV positive tumor status increases the tumoral expression of MHC1, which may support immunedetection and elimination by cytotoxic T-cells whilst hindering immunescape. This highlights the prognostic significance of a sufficient vitamin D supply among HNSCC-patients.

Publication History

Publication Date:
23 April 2019 (online)