Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.

Despite presenting a worse prognosis and being associated with highly aggressive tumors, triple-negative breast cancer (TNBC) is characterized by the higher frequency of tumor-infiltrating lymphocytes, which have been implicated in better overall survival and response to therapy. Though recent studies have reported the capacity of B lymphocytes to recognize overly-expressed normal proteins, and tumor-associated antigens, how tumor development potentially modifies B cell response is yet to be elucidated. Our findings reveal distinct effects of 4T1 and E0771 murine tumor development on B cells in secondary lymphoid organs. Notably, we observe a significant expansion of total B cells and plasma cells in the tumor-draining lymph nodes (tDLNs) as early as 7 days after tumor challenge in both murine models, whereas changes in the spleen are less pronounced. Surprisingly, within the tumor microenvironment (TME) of both models, we detect distinct B cell subpopulations, but tumor development does not appear to cause major alterations in their frequency over time. Furthermore, our investigation into B cell regulatory phenotypes highlights that the B10 Breg phenotype remains unaffected in the evaluated tissues. Most importantly, we identified an increase in CD19 + LAG-3 + cells in tDLNs of both murine models. Interestingly, although CD19 + LAG-3 + cells represent a minor subset of total B cells (< 3%) in all evaluated tissues, most of these cells exhibit elevated expression of IgD, suggesting that LAG-3 may serve as an activation marker for B cells. Corroborating with these findings, we detected distinct cell cycle and proliferation genes alongside LAG-3 analyzing scRNA-Seq data from a cohort of TNBC patients. More importantly, our study suggests that the presence of LAG-3 B cells in breast tumors could be associated with a good prognosis, as patients with higher levels of LAG-3 B cell transcripts had a longer progression-free interval (PFI). This novel insight could pave the way for targeted therapies that harness the unique properties of LAG-3 + B cells, potentially offering new avenues for improving patient outcomes in TNBC. Further research is warranted to unravel the mechanistic pathways of these cells and to validate their prognostic value in larger, diverse patient cohorts.

Câncer de mama: Reprogramação do metabolismo tumoral / Breast Cancer: tumoral metabolism reprogramming

O câncer de mama é a neoplasia de maior incidência em mulheres de todo o mundo, cuja mortalidade se deve principalmente ao desenvolvimento de metástases (condição patológica em que as células tumorais conseguem atravessar a matriz extracelular e se estabelecer em outros tecidos). Devido à importância epidemiológica dessa doença, estudos têm sido realizados em busca de uma melhor compreensão dos processos que atuam na carcinogênese e/ou tumorigênese e que, consequentemente, levam ao desenvolvimento de novas formas de diagnóstico e tratamento que sejam cada vez mais efetivos. Para manter a alta taxa de proliferação e desenvolver um perfil agressivo, características que são observadas em células tumorais, diversas alterações no metabolismo celular se tornam necessárias. O metabolismo tumoral começou a ser descrito por Otto Warburg em 1920, onde afirma que células cancerosas metabolizam glicose de forma diferente das células normais através da glicólise aeróbica. Dados recentes mostram que as alterações também ocorrem no metabolismo lipídico, apontando para uma reprogramação celular. A possibilidade de novos alvos farmacológicos inseriu o metabolismo como alvo das pesquisas recentes. Entretanto, e apesar do avanço, 90 anos depois da descoberta feita por Warburg, os estudos ainda não conseguiram esclarecer por completo como o metabolismo tumoral funciona, demonstrando assim a necessidade de mais pesquisas. Tendo em vista este cenário, essa revisão tem como objetivo documentar e discutir os principais resultados obtidos até o momento, como apontar e sugerir áreas de investigação. (AU)

Breast cancer is the most prevalent neoplasm in women worldwide, whose mortality is mainly due to the development of metastasis (pathological condition in which cancer cells can cross the extracellular matrix and settle in other tissues). Due to the epidemiological importance of this disease, studies have been carried out in order to better understand the processes involved in carcinogenesis and/or tumorigenesis and, consequently, allow the development of new forms of diagnosis and treatment that are increasingly effective. To maintain the high proliferation rate and develop an aggressive profile, features that are observed in tumor cells, several changes in cellular metabolism become necessary. Tumor metabolism began to be described by Otto Warburg in 1920, where he states that cancer cells metabolize glucose differently from normal cells through aerobic glycolysis. Recent data show that changes also occur in lipid metabolism, pointing to cellular reprogramming. The possibility of new pharmacological targets, inserted the metabolism as a target of recent research. However, despite the breakthrough, 90 years after Warburg discovery, studies have not yet been able to fully clarify how tumor metabolism works, demonstrating the need for more research. In view of this scenario, this review aims to document the main results obtained so far and to discuss those aspects that are not yet well understood. (AU)