4.6 Article

Tumor-Infiltrating CD20+ B Lymphocytes: Significance and Prognostic Implications in Oral Cancer Microenvironment

Journal

CANCERS
Volume 13, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/cancers13030395

Keywords

CD20; tumor-infiltrating B lymphocytes; prognosis; oral squamous cell carcinoma; immunohistochemistry

Categories

Funding

  1. Instituto de Salud Carlos III [PI19/01255, PI19/00560, CIBERONC CB16/12/00390]
  2. Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA)
  3. Ayudas a Grupos PCTI Principado de Asturias [IDI2018/155]
  4. Fundacion Bancaria Caja de Ahorros de Asturias-IUOPA
  5. FEDER from the European Union

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The study found that infiltrating CD20(+) B lymphocytes in oral squamous cell carcinoma (OSCC) are related to other immune subtypes and clinical prognosis, suggesting they may serve as an independent good prognostic factor in OSCC.
Simple Summary The complex interplay between the different cellular components in the tumor microenvironment (TME) dynamically modulates the antitumor immune response. This study investigates the prognostic relevance of CD20(+) tumor-infiltrating B lymphocytes in oral squamous cell carcinoma (OSCC), and also possible relationships with other immune subtypes and key players within the oral TME. Immunohistochemical analysis of stromal/tumoral CD20(+) B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4(+), CD8(+), and FOXP3(+) tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20(+) B lymphocytes and other immune profiles (i.e., CD4(+), CD8(+), and FOXP3(+) TILs, and CD68(+) and CD163(+) macrophages) both in stroma and tumor nests. Strikingly, CD20(+) TILs were inversely correlated with NANOG/SOX2 expression. Stromal CD20(+) TILs were significantly associated with T classification and second primary tumors. A stratified survival analysis showed that tumoral CD20(+) TILs were significantly associated with prognosis in male and younger patients, with tobacco or alcohol consumption, high tumoral CD8(+) TILs, low tumoral infiltration by CD68(+) macrophages, positive PD-L1 expression, and negative NANOG/SOX2. Multivariate Cox analysis further revealed clinical stage and tumoral CD20(+) TILs independently associated with disease-specific survival (HR = 2.42, p = 0.003; and HR = 0.57, p = 0.04, respectively). In conclusion, high CD20(+) TIL density emerges as an independent good prognostic factor in OSCC, suggesting a role in antitumor immunity. This study also uncovered an inverse correlation between CD20(+) TILs and CSC marker expression.

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