The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors.

The enthusiasm for immune checkpoint inhibitors (ICIs), an efficient tumor treatment model different from traditional treatment, is based on their unprecedented antitumor effect, but the occurrence of immune-related adverse events (irAEs) is an obstacle to the prospect of ICI treatment. IrAEs are a discrete toxicity caused by the nonspecific activation of the immune system and can affect almost all tissues and organs. Currently, research on biomarkers mainly focuses on the gastrointestinal tract, endocrine system, skin and lung. Several potential hypotheses concentrate on the overactivation of the immune system, excessive release of inflammatory cytokines, elevated levels of pre-existing autoantibodies, and presence of common antigens between tumors and normal tissues. This review lists the current biomarkers that might predict irAEs and their possible mechanisms for both nonspecific and organ-specific biomarkers. However, the prediction of irAEs remains a major clinical challenge to screen and identify patients who are susceptible to irAEs and likely to benefit from ICIs.

Efficacy and safety of neoadjuvant immunotherapy in resectable nonsmall cell lung cancer: A meta-analysis.

OBJECTIVE: Progress in neoadjuvant therapy for resectable nonsmall cell lung cancer(NSCLC1)has been stagnant. There have been great achievements in immunotherapy for advanced NSCLC, but the efficacy and safety of neoadjuvant immunotherapy for resectable NSCLC has not been clearly demonstrated. METHODS: Original articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable NSCLC published before January 2020 were retrieved from PubMed, Embase and Cochrane Library. The odds ratio (OR2) and 95 % confidence interval (CI3) were calculated. Heterogeneity and subgroup analysis were performed. RESULTS: A total of 252 patients from seven studies were included. Major pathological response (MPR4) and pathological complete response (pCR5) were used to evaluate the efficacy of neoadjuvant immunotherapy. Compared with neoadjuvant chemotherapy, which exhibited less than 25 % MPR and approximately 2 %-15 % pCR, the values in neoadjuvant immunotherapy were significantly higher (MPR: OR = 0.59; 95 % CI, 0.36-0.98; pCR: OR = 0.16; 95 % CI, 0.09-0.27). Safety was evaluated by the incidence of treatment-related adverse events (TRAE6), surgical resection rate, incidence of surgical complications and surgical delay rate. The pooled OR values of the incidence of TRAE, incidence of surgical complications and surgical delay rate were 0.19, 0.41 and 0.03, respectively, which were significantly better than those for neoadjuvant chemotherapy (95 % CI, 0.04-0.90; 0.22-0.75; 0.01-0.10, respectively). The mean surgical resection rate was 88.70 %, which was similar to the 75 %-90 % rate reported for neoadjuvant chemotherapy (OR = 7.61; 95 % CI, 4.90-11.81). CONCLUSION: Neoadjuvant immunotherapy is effective and safe for resectable NSCLC.