Unraveling LGALS1 as a Potential Immune Checkpoint and a Predictor of the Response to Anti-PD1 Therapy in Clear Cell Renal Carcinoma.

Immunotherapy base on immune checkpoint inhibitor had obtained significant progress in extending the survival of clear cell renal carcinoma (ccRCC) patients. In order to further improve the efficiency of immunotherapy, novel immune checkpoint inhibitors needed to be developed. Differentially expressed genes (DEGs) between healthy kidney tissues and ccRCC tissues had been found from GSE68417 by GEO2R online analysis tool. Correlation analysis and Kaplan-Meier survival analyses were based on UALCAN database. Analyses of the outcome of anti-PD1 treatment had been found from GSE67501 dataset. At first, 9 genes with higher expression were associated with shorter overall survival time. More importantly, higher expression of LGALS1 was correlated with a profitable outcome of anti-PD1 treatment and the combined the expression level of PD-L1 and LGALS1 together could more efficiently predict the outcome of anti-PD1 treatment than using PD-L1 alone. At last, the genes which correlated with LGALS1 expression in ccRCC patients were enriched in TNF alpha Signaling Pathway which is mainly correlated with T cell apoptosis and survival. Together, these suggest LGALS1 could be a potential immune checkpoint, which could promote tumor progression through affecting T cell survival.

Splenomegaly induced by anemia impairs T cell movement in the spleen partially via EPO.

The spleen is an important secondary lymph organ. Splenomegaly induced by anemia could affect the function of spleen in immune responses. We observe that anemia induced in mice with reduced peripheral T cell trafficking to the spleen T cell zones as well as CCL21 and CCL19 expression. In accordance with previous research, we found that the production of EPO in the mice kidney was sharply increased post anemia. In addition, mice were injected with different doses of EPO. Our results show that with the increased dosage of EPO, the chemokine expression in the spleen is lowered with a decrease in peripheral T cell homing to the spleen T cell zones. At last, our results show that the anemia mice model administrated with anti-EPO antibody had a higher expression of spleen CCL19 and CCL21 and an increased count of periphery T cells trafficking to spleen T cell zones at day 3 post induction. These data indicate that anemia could disturb T cell movement in the spleen, which might further affect T cell immune response, with partial involvement of EPO.