Recently, a distinct TIL-B subset (IgG4+CD49b+CD73+) was reported to express proangiogenic cytokines in patients with esophageal cancer and melanoma (34). within the tumor immune microenvironment and propose potential B cell-based immunotherapeutic strategies, which may help promote cancer immunotherapy. Keywords: B-lymphocytes, tumor-infiltrating lymphocytes, tertiary lymphoid structures, humoral immunity, immunotherapy, tumor microenvironment, prognosis Introduction The host immune system has proven to be a powerful tool functioning in Vandetanib trifluoroacetate cancer progression control (1). Owing to the direct tumor-killing effect of CD8+ cytotoxic T cells, T cell responses have become the driving force in the recent therapeutic advances in cancer management (2, 3). For example, chimeric antigen receptor-T (CAR-T) cell therapy has paved a new way in cancer treatment (2). CAR-T cell immunotherapy has achieved impressive strides in hematopoietic malignancies while exhibiting limited activity against solid tumors because of the poor infiltration and persistence of CAR-T cells and immunosuppressive microenvironment (2). Immune checkpoint blockade (ICB) has also been a major new approach to cancer immunotherapy which has been Vandetanib trifluoroacetate shown to enhance antitumor T cell immunity as its major mode of action (3). However, response rates of ICB remain relatively low, ranging from 15% to 40% based on cancer types (3). B cells are another major subpopulation of lymphocytes that mediate the humoral immunity of the adaptive immune system. However, they are often overlooked in the field of cancer immunotherapy, likely due to the general notion that humoral and cellular immunity tend to work in opposing fashions (4). Actually, B cells occupy a central position in forming the tumor immune microenvironment (4), and deserve far more attention to its diverse immune functions, both positive and negative. Both antitumor and tumor-promoting functions of B cells have been reported in tumor immunity and immunotherapy (4). Pdpn Evidence accumulating in Vandetanib trifluoroacetate the late 1990s facilitated a widespread acceptance of protumor functions mediated by B cells (5). However, more recent findings have shown that B cells employ a protective rather than a detrimental property in malignant diseases (6C13). Despite limited evidence regarding the negative prognostic value of tumor-infiltrating B lymphocytes (TIL-Bs), more recent cohort studies indicate the close Vandetanib trifluoroacetate association of elevated intratumoral B cells with prolonged survival of cancer patients (14). In this review, we highlight the latest findings of B cell biology in the tumor microenvironment (TME) as well as promising strategies targeting B cells, which may help promote cancer immunotherapy. TIL-B recruitment, location, and subsets Immune cells are recruited and infiltrate into tumor sites, forming a tumor immune microenvironment, where B cells comprise a considerable part of tumor-infiltrating lymphocytes (TILs). The recruitment of TIL-Bs into tumors is dependent on high endothelial venules (HEVs) (15), chemokines (16), and other immune cells (17). Vandetanib trifluoroacetate HEVs are postcapillary venules composed of plump endothelial cells, which allow entry of B lymphocytes into tertiary lymphoid structures (TLSs) (Figure?1) (15). In addition to HEVs, chemokines secreted by tumor cells and other immune components, such as CXCL2, CXCL20, and CXCL13, promote the influx of B cells into the tumor (16). Furthermore, CXCL13+CD103+CD8+ tumor-infiltrating T cells (TIL-Ts) were reported to correlate with B-cell recruitment in six cohorts of human tumors (17). In short, HEVs provide a channel for B cells to enter tumor niches, while T cells and multiple chemokines provide a driving force. Open in a separate window Figure?1 The migration pathways and diverse properties of TLS- and non-TLS-associated B cells in the TME. Na?ve B cells are recruited and infiltrate into the TME HEVs, mainly locating in the mantle zone of TLSs. After exposure to tumor antigens within the GCs, B cells interact with follicular helper T cells as well as follicular dendritic cells, and undergo a series of biological.
Recently, a distinct TIL-B subset (IgG4+CD49b+CD73+) was reported to express proangiogenic cytokines in patients with esophageal cancer and melanoma (34)
