A role for B cells in facilitating defense against an NK cell-sensitive lung metastatic tumor is revealed by stress

Abstract

Stressors impair immune defenses and pose risks among cancer patients. Natural Killer cells are not the sole immune defense against tumor development. Utilizing an NK-sensitive tumor model, this study evaluated immune effects to stress and determined whether lung metastasis resulted from B cells’ inability to augment tumorlytic function. Lung metastasis directly correlated with delayed lung B cell accumulation compared to NK, and T cells. Decreased interleukin-12 cytokine and CD80+ molecule expression by B cells correlated with decreased tumor lysis and increased tumor development. Thus, tumor defenses in the lung given stress exposure can depend on the B cell function.

B cells in tumor metastasis: friend or foe?

“…A higher TB score was associated with a better prognosis [19]. High infiltration of B cells was closely associated with a better prognosis in a variety of tumor types, including breast, ovarian, renal cell, thyroid papillary and lung cancers [20][21][22][23]. Furthermore, TIL-Bs were related to negative lymphatic invasion in gastric cancer, lymph node metastases in papillary thyroid carcinoma, and negative distant metastasis in colorectal cancer [23,24].…”

“…B cells activate natural killer (NK) cells by secreting IL-12. Studies on NK-sensitive metastatic lung cancer found that when lymphocyte infiltration at the lung metastasis site was reduced by a stress test, the reduction in B cells was particularly obvious, and the secretion of IL-12 by B cells was reduced, which weakened the activation and function of NK cells and then led to an increase in lung metastasis [21]. After neutralizing B cells with antibodies, tumor metastasis increased, and the effect was similar to that of neutralizing NK cells [42,43].…”

Regulatory B Cells—Immunopathological and Prognostic Potential in Humans

“…Breg-associated secretion of IgG4 promotes tumor growth [160,161] Granzyme B-expressing B cells in the microenvironment of various gynecological tumor diseases support immune tolerance to tumor antigens [24] Infiltration of tumors by Bregs as a negative predictor in breast, gastric, esophageal and squamous cell carcinomas in the head and neck region [31,[162][163][164][165] CD19 + CD24 + CD38 + Bregs as a negative prognostic factor in acute myeloid leukemia (AML) [166] Increased IL-10 production by CD19 + CD24 ++ CD27 + B cells in gastric carcinoma [31] STING-induced IL-35 + Bregs suppress NK cells in pancreas carcinoma [167] Increased number of CD19 + IL-10 + Bregs after surgery in patients with hepatocellular carcinoma (HCC) [168] Positive correlation between numbers of Bregs, regulatory T cells and TH17 cells as well as concentration of IL-10, IL-35 and BAFF in patients with primary hepatocellular carcinoma (PHC) [169,170]…”