As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4⁺ T cells, CD8⁺ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT. It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.

Chemotherapy is one of the main methods of cancer treatment and is known to induce autophagy in cancer cells. The main mechanism of chemotherapeutic agents is to promote apoptosis. In the process of chemotherapy, there is a unique association between autophagy and apoptosis. In this study, MDC staining, Hoechst 33342 staining and flow cytometry were used to explore the effects of autophagy on chemotherapy-induced apoptosis in A549 lung cancer cells and the association between autophagy and apoptosis was investigated via the addition of an autophagic inhibitor (3-methyladenine, 3-MA). This study demonstrated that cisplatin and paclitaxel were able to induce autophagy and apoptosis in A549 lung cancer cells and the inhibition of autophagy promoted cisplatin and paclitaxel‑induced apoptosis. Furthermore, autophagy may play a protective role in the processes of cisplatin and paclitaxel-induced apoptosis.

Background: Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. The use of neoadjuvant immunotherapy for the treatment of ESCC is gradually increasing. Camrelizumab is one such immune checkpoint inhibitor (ICI) used for treatment. In this retrospective study, we explored the efficacy, safety, and short-term perioperative prognosis of camrelizumab in combination with neoadjuvant chemotherapy for ESCC.Materials and Methods: A total of 254 Chinese patients with ESCC were enrolled in the study; 48 received camrelizumab in combination with neoadjuvant chemotherapy (C-NC group), and 206 received neoadjuvant chemotherapy (NC group). All patients underwent surgery after the completion of 2 cycles of neoadjuvant therapy.Results: Twenty patients (20/48, 41.7%) in the C-NC group and 22 patients (22/206, 10.7%) in the NC group achieved a pathologic complete response (pCR) (p<0.001). Twenty-nine patients (29/48, 60.4%) in the C-NC group and 56 patients (56/206, 27.2%) in the NC group achieved major pathologic remission (MPR) (p<0.001). There was a lower incidence of myelosuppression during neoadjuvant therapy in patients in the C-NC group (33/48, 68.8%) than in the NC group (174/206, 84.5%, p=0.012). The total incidence of adverse reactions during neoadjuvant therapy was also lower in the C-NC group (37/48, 77.1%) than in the NC group (189/206, 91.7%, p=0.003). Patients in the C-NC group had more lymph nodes cleared during surgery than those in the NC group (34 vs.30, p<0.001). The logistic model showed that the treatment regimen, age, and presence of lymph node metastasis were influential factors for achieving a pCR in these patients (p<0.001). Regarding other adverse events and surgery-related data, there were no significant differences observed between the two groups.Conclusion: Camrelizumab in combination with neoadjuvant chemotherapy is an efficacious neoadjuvant regimen with an acceptable safety profile and does not increase the difficulty of surgery or the incidence of complications. A pCR is more likely to be achieved in patients treated with camrelizumab in combination with neoadjuvant chemotherapy, in younger patients, or in those without lymph node metastases.

To investigate the potential role of microRNA-30a (miR-30a) in esophageal squamous cell carcinoma (ESCC). Expression of miR-30a-3p/5p was analyzed using microarray data and fresh ESCC tissue samples. Both in vitro and in vivo assays were used to investigate the effects of miR-30a-3p/5p on ESCC cell proliferation. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was performed to explore underlying mechanisms involved in ESCC, and then, assays were carried out to verify the potential molecular mechanism of miR-30a in ESCC. Low expression of miR-30a-3p/5p was closely associated with advanced ESCC progression and poor prognosis of patients with ESCC. Knock-down of miR-30a-3p/5p promoted ESCC cell proliferation. Increased miR-30a-3p/5p expression inhibited the Wnt signaling pathway by targeting Wnt2 and Fzd2. Down-regulation of miR-30a-3p/5p promotes ESCC cell proliferation by activating the Wnt signaling pathway through inhibition of Wnt2 and Fzd2.

The incidence of cutaneous melanoma (CM) has been increasing annually worldwide. In this study, we identify that MrgprF, a MAS related GPR family member, is decreased in cutaneous melanoma tissues and cell lines due to hypermethylation of its promoter region, and show that patients with CM expressing high levels of MrgprF exhibit an improved clinical outcome. We demonstrate that MrgprF forced expression inhibits tumor cell proliferation, migration, xenograft tumor growth, and metastasis. On the contrary, MrgprF knockdown promotes tumor cell proliferation and transformation of immortalized human keratinocyte-HaCaT cells, supporting the inhibitory role of MrgprF during tumor progression. Mechanistic studies reveal that MrgprF reduces the phosphoinositol‑3‑kinase (PI3K) complex formation between p101 and p110γ subunits, the critical step for phosphatidylinositol-(3, 4)-P2 (PIP2) conversion to phosphatidylinositol-(3, 4, 5)-P3 (PIP3), and then reduces the activation of PI3K/Akt signaling. This effect can be reversed by Akt specific agonist SC79. In addition, AMG 706, a previously documented inhibitor for endothelial cell proliferation, is identified as a potential agonist for MrgprF, and can impede tumor growth both in vitro and in vivo. Taken together, our findings suggest that MrgprF, a novel tumor suppressor in cutaneous melanoma, may be useful as a therapeutic target in the future.