Immunoprofiling is useful for predicting prognosis in various malignancies and provides targets for immunotherapy. Quantitative multispectral imaging system, which allows simultaneous detection of multiple immune markers, is a novel method for examining the tumor immune environment. We compared the expression levels of various surface markers in immune cells between colitis-associated cancer (CAC) and sporadic colorectal cancer (CRC) and evaluated the clinical usefulness of immunoprofiling in CRC. Tumor specimens from 24 CAC patients and 48 sporadic CRC patients, matched by age, sex, and tumor location to CAC, were included in the analysis. The expression levels of CD3, CD8, Foxp3, and programmed death-ligand 1 (PD-L1) in immune cells at the invasive margins of tumor tissues were evaluated by quantitative multispectral imaging. The CAC group had significantly less levels of cells expressing CD3, CD8, Foxp3, or PD-L1 (all, p < 0.01). In the CAC group, patients whose immune cells had high expression of CD3 + and CD8 + had better overall survival. The immune profiling patterns of CAC patients were significantly distinct from those of sporadic CRC patients, suggesting that CAC and sporadic CRC have distinct disease phenotypes. Immunoprofiling can be helpful for evaluation of clinical prognosis in CAC.

Crizotinib is a clinically approved tyrosine kinase inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EML4-ALK fusion. Crizotinib was originally developed as an inhibitor of MET (HGF receptor), which is involved in the metastatic cascade. However, little is known about whether crizotinib inhibits tumor metastasis in NSCLC cells. In this study, we found that crizotinib suppressed TGFβ signaling by blocking Smad phosphorylation in an ALK/MET/RON/ROS1-independent manner in NSCLC cells. Molecular docking and in vitro enzyme activity assays showed that crizotinib directly inhibited the kinase activity of TGFβ receptor I through a competitive inhibition mode. Cell tracking, scratch wound, and transwell migration assays showed that crizotinib simultaneously inhibited TGFβ- and HGF-mediated NSCLC cell migration and invasion. In addition, in vivo bioluminescence imaging analysis showed that crizotinib suppressed the metastatic capacity of NSCLC cells. Our results demonstrate that crizotinib attenuates cancer metastasis by inhibiting TGFβ signaling in NSCLC cells. Therefore, our findings will help to advance our understanding of the anticancer action of crizotinib and provide insight into future clinical investigations.