Manipulation of tumour-infiltrating B cells and tertiary lymphoid structures: a novel anti-cancer treatment avenue?

Abstract

Combining different standard therapies with immunotherapy for the treatment of solid tumours has proven to yield a greater clinical benefit than when each is applied separately; however, the percentage of complete responses is still far from optimal, and there is an urgent need for improved treatment modalities. The latest literature data suggest that tertiary lymphoid structures (TLS), previously shown to correlate with the severity of autoimmune diseases or transplant rejection, are also formed in tumours, have a significant beneficial effect on survival and might reflect the generation of an effective immune response in close proximity to the tumour. Thus, the facilitation of TLS formation in tumour stroma could provide novel means to improve the efficiency of immunotherapy and other standard therapies. However, little is known about the mechanisms regulating the formation of tumour-associated TLS. Studies of chronic inflammatory diseases and transplant rejection have demonstrated that TLS formation and/or function requires the presence of B cells. Additionally, the infiltration of B cells into the tumour stroma has been demonstrated to be a significant prognostic factor for improved survival in different human tumours. This suggests that B cells could play a beneficial role in anti-tumour immune response not only in the context of antibody production, antigen presentation and Th1-promoting cytokine production, but also TLS formation. This review focuses on the latest discoveries in tumour-infiltrating B cell functions, their role in TLS formation and relevance in human tumour control, revealing novel opportunities to improve cancer therapies.

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

“…Up to date, most reports in the literature state a positive effect of TILs in respect to OS, relapse-free survival and association with favorable prognostic factors, as well as lower T-stage (8). High B-cell density is said to be associated with improved outcome in gastric, breast and colorectal cancer (9)(10)(11), as well as squamous cell carcinoma of the tongue (12), melanoma and hepatocellular carcinoma (5,13).…”

Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery

“…Some immune cells have pro-tumorigenic activity, whereas others are anti-tumorigenic. B lymphocytes have been ascribed both pro-and anti-tumorigenic activities [3][4][5]. Many functional types of B cells that affect tumor growth or dissemination have now been identified, including B cells that support Th1 cells and cytotoxic T lymphocytes, B cells that promote angiogenesis, B regulatory cells that both suppress T effector cells and support T regulatory cells, and B cells that express class-switched, affinitymatured antibodies [5].…”

Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer

“…However, based on a limited cohort of 28 cases, our study revealed novel characteristics of TILs and thus establishes the presence of TLS in bladder tumours in addition to their significant association with MIBC. TLS containing [22,23]. In ovarian, colorectal, breast and lung cancer, intra-tumoural B cells or those located within organized TLS are associated with favorable outcomes suggesting there anti-tumour role whereas their increased numbers are negatively correlated with melanoma, prostate, renal cell and hepatocellular carcinoma prognosis [16,19,24].…”