Abstract: With the improvement of people's living standards, gastrointestinal adverse reactions caused by various adverse factors have attracted more and more people's attention. A recent study has indicated that coronavirus disease 2019 (COVID-19) could also invade the gastrointestinal tract, leading to gastrointestinal adverse reactions (Song et al., 2020). In recent years, immunotherapy has provided certain effects for some patients with advanced malignant tumors. A microencapsulation of immunoglobulin Y (IgY) was reported to provide an effective way to preserve IgY and improve its performance in the gastrointestinal tract (Zhang J et al., 2020). Immune checkpoint inhibitors (ICIs) can significantly improve the survival of some advanced malignant tumors, especially metastatic malignant melanoma and lung cancer (Afzal et al., 2018; Madden and Kasler, 2019). They include anti-cytotoxic T lymphocyte-associated antigen-4 (anti-CTLA-4) antibodies (ipilimumab and tremelimumab), anti-programmed cell death protein 1 (anti-PD-1) antibodies (nivolumab and pembrolizumab), and anti-programmed death-ligand 1 (anti-PD-L1) antibodies (atezolizumab, avelumab, and durvalumab) (Baxi et al., 2018). Previous studies have shown that ICI combination therapy, such as nivolumab plus ipilimumab, has particular efficacy in lung cancer, renal cell carcinoma, and malignant melanoma (Wolchok et al., 2017; Derosa et al., 2018; Doroshow et al., 2019). However, ICIs may also lead to many immune-related adverse events (irAEs), even causing severe complications in certain cases. The most well-established toxicities from ICI therapy are gastrointestinal irAEs, including enteritis, enterocolitis, microscopic colitis, and gastritis, which have attracted public attention in recent years; reports of such events associated with ICI therapy also have increased (Tandon et al., 2018; de Malet et al., 2019). These gastrointestinal irAEs may generally respond well to corticosteroids and infliximab (Haanen et al., 2017). Although most of these irAEs are low-grade, a lack of detection and timely treatment may incur severe or fatal complications.

与免疫检查点抑制剂相关的胃肠道毒性：利用WHO药物不良反应数据库VigiBase进行的不成比例分析.

[1]Abu-Sbeih H, Wang YH, 2020. Gastrointestinal tract adverse events. In: Naing A, Hajjar J (Eds.), Immunotherapy. Springer, Cham, p.247-253.

[2]Afzal MZ, Mercado RR, Shirai K, 2018. Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma. J Immunother Cancer, 6:64.

[3]Baxi S, Yang A, Gennarelli RL, et al., 2018. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ, 360:k793.

[4]Cho JH, Choi JH, 2020. Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: a case report. World J Clin Cases, 8(3):552-559.

[5]de Malet A, Antoni G, Collins M, et al., 2019. Evolution and recurrence of gastrointestinal immune-related adverse events induced by immune checkpoint inhibitors. Eur J Cancer, 106:106-114.

[6]Derosa L, Hellmann MD, Spaziano M, et al., 2018. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol, 29(6):1437-1444.

[7]Doroshow DB, Sanmamed MF, Hastings K, et al., 2019. Immunotherapy in non-small cell lung cancer: facts and hopes. Clin Cancer Res, 25(15):4592-4602.

[8]Gu LH, Khadaroo PA, Su H, et al., 2019. The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis. BMC Cancer, 19:559.

[9]JBAG Haanen, Carbonnel F, Robert C, et al., 2017. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 28(Suppl_4):iv119-iv 142.

[10]Leppkes M, Ganslmayer M, Strauß R, et al., 2015. Das toxic megacolon. Med Klin Intensivmed Notfmed, 110(7):500-505.

[11]Madden K, Kasler MK, 2019. Immune checkpoint inhibitors in lung cancer and melanoma. Semin Oncol Nurs, 35(5):150932.

[12]Rodriguez-Vida A, Perez-Gracia JL, Bellmunt J, 2018. Immunotherapy combinations and sequences in urothelial cancer: facts and hopes. Clin Cancer Res, 24(24):6115-6124.

[13]Sangro B, Chan SL, Meyer T, et al., 2020. Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma. J Hepatol, 72(2):320-341.

[14]Song M, Li ZL, Zhou YJ, et al., 2020. Gastrointestinal involvement of COVID-19 and potential faecal transmission of SARS-CoV-2. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(9):749-751.

[15]Tandon P, Bourassa-Blanchette S, Bishay K, et al., 2018. The risk of diarrhea and colitis in patients with advanced melanoma undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis. J Immunother, 41(3):101-108.

[16]Wang DY, Ye F, Zhao SL, et al., 2017. Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: a systematic review and meta-analysis. Oncoimmunology, 6(10):e1344805.

[17]Wang DY, Salem JE, Cohen JV, et al., 2018. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol, 4(12):1721-1728.

[18]Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al., 2017. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med, 377(14):1345-1356.

[19]Xu C, Chen YP, Du XJ, et al., 2018. Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ, 363:k4226.

[20]Yuan ZH, Yang HK, Wei YM, 2019. Combined induction with anti-PD-1 and anti-CTLA-4 antibodies provides synergistic antitumor effects in DC-CIK cells in renal carcinoma cell lines. Int J Clin Exp Pathol, 12(1):123-132.

[21]Zhang J, Li HH, Chen YF, et al., 2020. Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(8):611-627.

[22]Zhang ML, Neyaz A, Patil D, et al., 2020. Immune-related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies. Histopathology, 76(2):233-243.

[23]Zhao SZ, Reynolds MW, Lefkowith J, et al., 2001. A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organization/Uppsala Monitoring Centre safety database. Clin Ther, 23(9):1478-1491.