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The side effects of platinum-based chemotherapy are important factors limiting the survival of oral squamous cell carcinoma (OSCC) patients. Current research suggests that pyroptosis is involved in this process. However, how this mechanism can be used to reduce side effects has not yet been elucidated. In this study, we reported that GSDME was expressed at higher levels in normal tissues than in cancerous tissues in OSCC patients and was the main cause of platinum-based side effects. In an OSCC xenograft model, the inflammatory status and GSDME expression were increased after cisplatin chemotherapy. Cellular experiments showed that higher expression of GSDME was associated with less chemoresistance to cisplatin. A subsequent study demonstrated that cisplatin treatment promotes the maturation of caspase-3, triggers GSDME-mediated pyroptosis and induces cell death. When the amino acid sequence of GSDME cleaved by caspase-3 was mutated, cellular death and pyroptosis induced by cisplatin were significantly inhibited. Moreover, application of vitamin D during cisplatin-based chemotherapy could successfully inhibit GSDME cleavage and pyroptotic cell death in vitro and in vivo. Taken together, our study revealed that vitamin D can inhibit caspase-3-mediated GSDME cleavage and thus reduce normal tissue pyroptosis, relieving chemotherapeutic side effects. Inhibition of systemic GSDME during chemotherapy is currently unachievable. Vitamin D supplementation during chemotherapy in OSCC patients might be able to reduce the process described above and benefit patients. However, additional follow-up clinical studies are needed.There is a discrepancy in the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment for advanced lung adenocarcinoma (LUAD) patients with EGFR sensitizing mutations (mEGFR). Molecular markers other than mEGFR remain to be investigated to better predict EGFR-TKI efficacy. Here, 49 LUAD patients with mEGFR (19 deletions or 21 L858R mutations) who received the first-generation EGFR-TKI icotinib therapy were included and stratified into 25 good-responders with a progression-free survival (PFS) longer than 11 months and 24 poor-responders with a PFS shorter than 11 months. We conducted targeted metabolomic detection and next-generation sequencing on serum and tissue samples, respectively. Subsequently, two metabolomic profiling-based discriminant models were constructed for icotinib efficacy prediction, 10 metabolites overlapped in both models ensured high credibility for distinguishing good- and poor-responders. Seven of the 10 metabolites displayed significant differences beurrently mutated genes and the 4 metabolites related metabolic genes in glycerophospholipid metabolism and sphingolipid metabolism pathways. This study demonstrated that lipids metabolism and concurrently mutated genes with mEGFR were associated with the icotinib efficacy, which provides novel perspectives in classifying clinical responses of mEGFR LUAD patients and reveals the potential of non-invasive pretreatment serum metabolites in predicting EGFR-TKI efficacy.EGFR tyrosine kinase inhibitors (TKIs) are the first-line drugs for NSCLC. But, the acquired resistance limited their efficacy, so that the patients deteriorate eventually. Therefore, it is necessary to clarify the mechanism of the acquired resistance and overcome it for effective NSCLC therapy. In this experimental study, a stable gefitinib resistant lung adenocarcinoma cell line (PC9/GR) infected with shRNA-c-kit-homo-1386 were established; c-kit siRNA and c-kit inhibitors were used to block c-kit signaling; the acquired resistance of PC9/GR cells and the effects of c-kit siRNA and c-kit inhibitors on the growth and invasion of PC9/GR cells were investigated with CCK-8 assay, colony formation and cell invasion assays in vitro; the tumor growth inhibition effects of c-kit inhibitors on PC9/GR cell generated tumors were tested in vivo; the mechanisms involved in the acquired resistance reverse, growth and invasion inhibition effects of c-kit siRNA and c-kit inhibitors on PC9/GR cells were evaluated with qRT-P c-kit signaling mediated the acquired gefitinib resistance, cell growth, invasion, stemness and EMT phenotype of PC9/GR cells. Targeting c-kit signaling with c-kit siRNA and small molecule c-kit inhibitors might overcome the acquired gefitinib resistance, and inhibit PC9/GR cell growth in vitro and in vivo.Cytotoxic CD8+ T cell exhaustion is one of the mechanisms underlying the tumor immune escape. The paradigm-shifting immune checkpoint therapy can mitigate CD8+ T lymphocyte exhaustion, reinvigorate the anticancer immunity, and achieve durable tumor regression for some patients. Emerging evidence indicates that CD4+ T lymphocytes also have a critical role in anticancer immunity, either by directly applying cytotoxicity toward cancer cells or as a helper to augment CD8+ T cell cytotoxicity. Whether anticancer CD4+ T lymphocytes undergo exhaustion during immunotherapy of solid tumors remains unknown. Here we report that melanoma antigen TRP-1/gp75-specific CD4+ T lymphocytes exhibit an exhaustion phenotype after being adoptively transferred into mice bearing large subcutaneous melanoma. Exhaustion of these CD4+ T lymphocytes is accompanied with reduced cytokine release and increased expression of inhibitory receptors, resulting in loss of tumor control. Importantly, we demonstrate that PD-L1 immune checkpoint blockade can prevent exhaustion, induce proliferation of the CD4+ T lymphocytes, and consequently prevent tumor recurrence. Therefore, when encountering an excessive amount of tumor antigens, tumor-reactive CD4+ T lymphocytes also enter the exhaustion state, which can be prevented by immune checkpoint blockade. AZD5363 datasheet Our results highlight the importance of tumor-specific CD4+ T lymphocytes in antitumor immunity and suggest that the current immune checkpoint blockade therapy may achieve durable anticancer efficacy by rejuvenating both tumor antigen-specific CD8+ T lymphocytes and CD4+ T lymphocytes.The nucleic acid guanine-quadruplex structures (G4s) are involved in many aspects of cancer progression. The DEAH-box polypeptide 36 (DHX36) has been identified as a dominant nucleic acid helicase which targets and disrupts DNA and RNA G4s in an ATP-dependent manner. However, the actual role of DHX36 in breast cancer remains unknown. In this study, we observed that the gene expression of DHX36 was positively associated with patient survival in breast cancer. The abundance of DHX36 is also linked with pathologic conditions and the stage of breast cancer. By using the xenograft mouse model, we demonstrated that the stable knockdown of DHX36 via lentivirus in breast cancer cells significantly promoted tumour growth. We also found that, after the DHX36 knockdown (KD), the invasion of triple-negative breast cancer cells was enhanced. In addition, we found a significant increase in the number of cells in the S-phase and a reduction of apoptosis with the response to cisplatin. DHX36 KD also desensitized the cytotoxic cellular response to paclitaxel and cisplatin.