OncoImmunology (Mar 2019)

Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma

  • Axel Lechner,
  • Hans A. Schlößer,
  • Martin Thelen,
  • Kerstin Wennhold,
  • Sacha I. Rothschild,
  • Ramona Gilles,
  • Alexander Quaas,
  • Oliver G. Siefer,
  • Christian U. Huebbers,
  • Engin Cukuroglu,
  • Jonathan Göke,
  • Axel Hillmer,
  • Birgit Gathof,
  • Moritz F. Meyer,
  • Jens P. Klussmann,
  • Alexander Shimabukuro-Vornhagen,
  • Sebastian Theurich,
  • Dirk Beutner,
  • Michael von Bergwelt-Baildon

Journal volume & issue
Vol. 8, no. 3


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B lymphocytes are important players in immune responses to cancer. However, their composition and function in head and neck squamous cell carcinoma (HNSCC) has not been well described. Here, we analyzed B cell subsets in HNSCC (n = 38), non-cancerous mucosa (n = 14) and peripheral blood from HNSCC patients (n = 38) and healthy controls (n = 20) by flow cytometry. Intratumoral B cells contained high percentages of activated (CD86+), antigen-presenting (CD86+/CD21−) and memory B cells (IgD−/CD27+). T follicular helper cells (CD4+/CXCR5+/CD45RA−/CCR7−) as key components of tertiary lymphoid structures and plasma cells made up high percentages of the lymphocyte infiltrate. Percentages of regulatory B cell varied depending on the regulatory phenotype. Analysis of humoral immune responses against 23 tumor-associated antigens (TAA) showed reactivity against at least one antigen in 56% of HNSCC patients. Reactivity was less frequent in human papillomavirus associated (HPV+) patients and healthy controls compared to HPV negative (HPV−) HNSCC. Likewise, patients with early stage HNSCC or MHC-I loss on tumor cells had low TAA responses. Patients with TAA responses showed CD4+ dominated T cell infiltration compared to mainly CD8+ T cells in tumors without detected TAA response. To summarize, our data demonstrates different immune infiltration patterns in relation to serological TAA response detection and the presence of B cell subpopulations in HNSCC that can engage in tumor promoting and antitumor activity. In view of increasing use of immunotherapeutic approaches, it will be important to include B cells into comprehensive phenotypic and functional analyses of tumor-associated lymphocytes.