白细胞介素-36α通过增强 CD8(+) T 淋巴细胞的浸润和活性抑制结直肠癌转移

Colorectal cancer is one of the deadliest cancers, and the discovery of new diagnostic biomarkers and therapeutic targets is vital. Interleukin-36α (IL-36α) is a proinflammatory factor that can initiate the inflammatory response and promote the systemic T helper-1 (Th1) immune response. In this study, we investigated the immunological role of IL-36α in CRC.

We found that IL-36α was downregulated in human CRC tissues. Patients with high IL-36α levels showed better survival and low IL-36α expression was significantly associated with greater tumor distal metastasis and TNM stage.

We constructed two cell lines overexpressing IL-36α (CT26-IL-36α and HT29-IL-36α cells). In vitro assays revealed that IL-36α overexpression reduced the proliferation, migration, and invasion of CT26-IL-36α, and HT29-IL-36α cells. Using CT26-vector and CT26-IL-36α tumor mouse model and lung metastasis models, we found that IL-36α overexpression elicited a significant antitumor effect and inhibited lung metastasis in vivo.

These inhibitory effects were associated with an increase in the number of CD3 + CD8 + T lymphocytes within the tumor tissue as well as increased cytokine production in CD8 + T lymphocytes present in the tumor, spleen, and draining lymph nodes.

Furthermore, we revealed that CT26-IL-36α cells enhanced the secretion of CXCL10 and CXCL11 from chemotactic CD8 + T lymphocytes, as compared with CT26-vector cells. Taken together, these results suggest that IL-36α is a promising therapeutic agent for targeting CRC by promoting the activation, proliferation, and tumor infiltration of T lymphocytes.