T Follicular helper cells expansion during colon and mammary tumor development

MONTANA N. MANSELLE COCCO; NICOLÁS SARBIA; RAMIRO PERROTA; TOMAS D'ALOTTO; ADA BLIDNER; FLORENCIA VEIGAS; ROMINA GIROTTI; MARIANA SALATINO; GABRIEL A RABINOVICH; MARTA A. TOSCANO

San Pablo

Conferencia; Second AACR International Conference; 2018

AACR LACOG

T Follicular helper (TFh) cells are essential for the activation and differentiation of B cells and the development of humoral immunity. By promoting the formation of the germinal centers, TFh cells contribute to the differentiation of long-lived plasma cells and to the production of high affinity antibodies. Several studies have suggested that the frequency and distribution of TFh cells may constitute novel diagnosis and prognosis biomarkers in autoimmune and neoplastic diseases. In this regard, high frequency of TFh cells have been observed in peripheral blood of patients with advanced non-small cell lung cancer and tumor infiltrates of patients with breast cancer and colorectal cancer. However, the relevance of TFh cells in tumor progression has not yet been studied in depth. Galectin-1 (Gal-1), a soluble glycan binding protein, is implicated in the regulation of the biology of immune and endothelial cells. In particular, Gal-1 promotes an immunoregulatory phenotype on T cells, dendritic cells and macrophages and induces tumor angiogenesis.In this study, we analyzed whether the frequency of TFh lymphocytes varies during tumor growth and whether tumor Gal-1 has any impact on the TFh subpopulation. We used three murine tumor models, the 4T1 mammary tumor, the CT26 colon carcinoma and GG41 melanoma tumor. We found that the presence of 4T1 and CT26 tumors promoted an increase in the frequency of TFh cells in tumor-draining lymph nodes (TDLN) as compared to tumor free mice. In contrast, development of GG41 tumors did not promote such induction. Interestingly, the increase in the TFh subpopulation was accompanied with an increase in the percentage of CD19+B220+ B cells in the TDLN of the 4T1 model and a concomitant reduction in the percentage of total CD4+ cells, suggesting that the enrichment of TFh cells in 4T1 might contribute to B cell expansion. When we then analyzed intratumoral lymphocytes we observed that both the CT26 and the 4T1 tumors were highly infiltrated with CD4+ T cells (~20%) while GG41 tumors displayed a reduced frequency of CD4 infiltration (