The Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: on Subsets and Subsites

Niels E Wondergem, Irene H Nauta, Tara Muijlwijk, C René Leemans, Rieneke van de Ven, Niels E Wondergem, Irene H Nauta, Tara Muijlwijk, C René Leemans, Rieneke van de Ven

Abstract

Purpose: To understand why some patients respond to immunotherapy but many do not, a clear picture of the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is key. Here we review the current understanding on the immune composition per HNSCC subsite, the importance of the tumor's etiology and the prognostic power of specific immune cells.

Recent findings: Large cohort data are mostly based on deconvolution of transcriptional databases. Studies focusing on infiltrate localization often entail small cohorts, a mixture of HNSCC subsites, or focus on a single immune marker rather than the interaction between cells within the TME. Conclusions on the prognostic impact of specific immune cells in HNSCC are hampered by the use of heterogeneous or small cohorts. To move forward, the field should focus on deciphering the immune composition per HNSCC subsite, in powered cohorts and considering the molecular diversity in this disease.

Keywords: HNSCC subsites; Head and neck squamous cell carcinoma; Innate and adaptive immune system; Prognosis; Tumor infiltrating lymphocytes; Tumor microenvironment.

Conflict of interest statement

Niels Wondergem has conducted clinical trials with Bristol-Myers Squibb.

Irene Nauta declares that she has no conflict of interest.

Tara Muijlwijk declares that she has no conflict of interest.

Rieneke van de Ven declares she receives research funding from Genmab BV.

René Leemans has conducted clinical trials with Bristol-Myers Squibb and is on the global advisory board of Merck & Co., Inc. and Rakuten Medical advisory board.

Figures

Fig. 1
Fig. 1
Schematic overview of the current understanding on the differences between the immune cells infiltrating HPV-related (a) and HPV-unrelated (b) HNSCC. Abbreviations: CAF: cancer associated fibroblast; pDC: plasmacytoid dendritic cell; mDC: myeloid dendritic cell; NK cell: natural killer cell; M1: M1 macrophage; M2: M2 macrophage

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