Abundance of Tumor-Infiltrating B Cells in Human Epithelial Malignancies

Abstract

Cancer is a major global health problem. The type of malignant neoplasm and the potency of the immune response against tumors are two of the key factors influencing the outcome of the disease. The degree of tumor infiltration by lymphocytes plays an important role in antitumor response development, generally correlating with a favorable prognosis of treatment for certain cancers. We analyzed the abundance of tumor-infiltrating B cells (TIBs) in solid tumors of different cancers. TIBs were shown to be more abundant in colon and sigmoid colon cancer samples compared with cecal, rectal, and kidney cancer samples. The median and interquartile range of the TIB fraction were 11.5% and 4-20% in colon cancer, 6% and 3-11% in sigmoid colon cancer, 2.7% and 0.7-3.7% in cecal cancer, 2.5% and 0.9-3.6% in rectal cancer, 1.4% and 1.0-2.3% in kidney cancer, and 3.0% and 1.8-12% in lung cancer, respectively. However, there were no significant differences in the abundance of TIBs among samples at different stages of the cancer. Hence, investigation of the B cell response in colon cancer is of particular interest, since increased quantities of TIBs may indicate the existence of immunogenic tumor markers or the cell-cell interactions involved in disease progression. We believe that studying the diversity of TIBs in colon cancer will increaseour understanding of the mechanisms of the disease, contributing to the identification of new molecular targets for targeted oncotherapy.

Keywords: colorectal cancer; solid tumors; tumor-infiltrating B cells.

Fig. 1

Tumor tissue dissociation workflow

Fig. 2

Sequential gating strategy for assessing the fraction of tumor-infiltrating B cells. (A) The oval area denotes cells assigned to the tumor cell population based on lateral and forward light scattering data. (B) The oval area highlights single cells. (C) The rectangular area denotes the living cell population. (D) The image is divided into quadrants that are related to the CD45–/CD19–, CD45–/CD19+, CD45+/CD19–, and CD45+/CD19+ cell subsets. The CD45+/ CD19+ cell subset corresponds to B cells

Fig. 3

(A) Quantification of tumor-infiltrating B cells in tumor material of various nosologies. (B) Abundance of tumor-infiltrating B cells in colon cancer samples, depending on the stage. Statistical analysis was performed using the nonparametric Mann–Whitney U test. *P < 0.05; NS – no significant difference