A B‐cell or a key player? The different roles of B‐cells and antibodies in melanoma

Abstract

The B‐cell system plays an important role in the melanoma immune response; however, consensus has yet to be reached in many facets. Here, we comprehensively review human studies only, due to fundamental differences in the humoral response with animal models. Tumour‐infiltrating B‐cells are associated with contradictory prognostic values, reflecting a lack of agreement between studies on cell subset classification and differences in the markers used, particularly the common use of a single marker not differentiating multiple subsets. Tertiary lymphoid structures (TLS) organise T‐cells and B‐cells within tumours to generate a local anti‐tumour response and TLS presence associates with improved survival in response to immune checkpoint blockade, in late‐stage disease. Autoantibody production is increased in melanoma patients and has been proposed as biomarkers for diagnosis, prognosis and treatment/toxicity response; however, no consistent targets are yet identified. The function of antibodies in an anti‐tumour response is determined by its isotype and subclass; IgG4 is immune‐suppressive and robustly correlate with poor patient survival in melanoma. We conclude that the current B‐cell literature needs careful interpretation based on the methods used and that we need a consensus of markers to define B‐cells and associated lymphoid organs. Furthermore, future studies need to not only examine antibody targets, but also isotypes when considering functional roles.

Case Report: Longitudinal Evaluation and Treatment of a Melanoma-Associated Retinopathy Patient

“…Melanocytes, the pigment-producing cells of the skin that become cancerous in CM, are one of few cell types outside the eye that express TRPM1 (Deeds et al, 2000;Duncan et al, 2001Duncan et al, , 1998Fang and Setaluri, 2000). In MAR patients, B cells produce antibodies against melanocyte antigens, including TRPM1 (Dhingra et al, 2011;Kinker et al, 2021;Rodgers et al, 2022). Consequently, these circulating autoantibodies disrupt vision when they in ltrate the retina and bind TRPM1 in ON-BCs (Lei et al, 2000;Xiong et al, 2013).…”

Lymphoblastoid cell lines do not recapitulate physiological circulating B cell subtypes

“…the longer lived matured humoral immune cells. Markers to identify specific B cell subtypes along this pathway have been identified but their expression levels are often less well defined between subtypes and have been inconsistently applied across studies ( Rodgers et al, 2022 ).…”

“…Historically, the core markers used to define many of the specific physiological B cell subtypes have differed between studies (as summarised by Sanz et al (2019) ) and reviewed in the context of melanoma associated B cells ( Rodgers et al, 2022 )), which makes comparison of B cell subtypes between a large number of studies difficult. The question of whether some B cell phenotyping markers can be applied to the characterisation of LCLs has previously been explored ( Supplementary Table 1 ).…”