Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin ß7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2).

Background: Stanniocalcin-2 (STC2) is a secreted glycoprotein which plays an important role in regulating the homeostasis of calcium, glucose homeostasis, and phosphorus metastasis. Accumulating evidence suggests that STC2 is implicated in cancer mechanisms. However, the effects of STC2 on cancer development and progression across pan-cancer are not yet completely known. Methods: Data were downloaded from The Cancer Genome Atlas database to obtain differentially expressed genes significantly associated with prognosis (key genes). A gene was selected for subsequent correlation studies by integrating the significance of prognosis and the time-dependent ROC curve. Gene expression of different tumor types was analyzed based on the UCSC XENA website. Furthermore, our study investigated the correlation of STC2 expression between prognosis, immune cell infiltration, immune checkpoint genes (ICGs), mismatch repair genes (MMRs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity in various malignant tumors. Gene set enrichment analysis (GSEA) was conducted for correlated genes of STC2 to explore potential mechanisms. Results: A total of 3,429 differentially expressed genes and 397 prognosis-related genes were identified from the TCGA database. Twenty-six key genes were found by crossing the former and the latter, and the highest risk gene, STC2, was selected for subsequent correlation studies. STC2 had good diagnostic performance for HNSCC, and was closely related to the survival status and clinicopathological stage of HNSCC patients. In pan-cancer analysis, STC2 was upregulated in 20 cancers and downregulated in seven cancers. STC2 overexpression was overall negatively correlated with overall survival, disease-free survival, disease-specific survival, and progress-free survival. STC2 was profoundly correlated with the tumor immune microenvironment, including immune cell infiltration, ICGs, MMRs, TMB, and MSI. Moreover, STC2 was significantly negatively correlated with the sensitivity or resistance of multiple drugs. Conclusion: STC2 was a potential prognostic biomarker for pan-cancer and a new immunotherapy target.