HPV+ head and neck squamous cell carcinomas exhibited diverse tumor-infiltrating B-cell subsets.

  • Major Finding: HPV+ head and neck squamous cell carcinomas exhibited diverse tumor-infiltrating B-cell subsets.

  • Concept: B cells in the tumor microenvironment were HPV antigen–specific and had signs of chronic exposure.

  • Impact: This study intricately characterizes B cells in these tumors and suggests how they may be harnessed.

Although B cells and plasma cells are commonly found in the tumor microenvironment (TME), their roles have not been fully established, and whether they could be harnessed for anticancer therapies is unclear. To investigate this, Wieland and colleagues analyzed surgically resected samples from human papillomavirus (HPV)–positive head and neck squamous-cell carcinomas (HNSCC), first establishing that antibody-secreting cells in the TME produced HPV antigen–specific IgG antibodies, most often targeting the viral protein E2. Additionally, plasma titers of HPV antigen–specific IgG antibodies correlated with the presence of antibody-secreting cells specific to those antigens in the TME. Further analyses showed that the TME contained HPV antigen–specific activated B cells, a proliferating B-cell subtype committed to the memory B-cell lineage that was previously identified in the peripheral blood following vaccination or infection, a finding supporting the presence of chronic antigen exposure. Single-cell RNA-sequencing experiments revealed that the TME contained several types of antigen-experienced B cells, including antibody-secreting cells, activated B cells, and germinal center B cells. Overall, B cells (including activated B cells) were preferentially found in tumor stroma, where they formed clusters indicative of ongoing germinal center reactions, rather than the parenchyma. Similar trends in B-cell localization were observed in HPV-negative HNSCCs, but lymphocyte infiltration of these tumors was strikingly lower than that of HPV-positive HNSCCs. In summary, this work provides an intricate characterization of B cells in the TME of HPV-positive HNSCC, including their antigen specificity, and provides clues regarding how these B cells may be exploited for anticancer therapies.

Wieland A, Patel MR, Cardenas MA, Eberhardt CS, Hudson WH, Obeng RC, et al. Defining HPV-specific B cell responses in patients with head and neck cancer. Nature 2020 Nov 18 [Epub ahead of print].

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