免疫检查点抑制剂已经在先进和转移性癌症的治疗上引发了一场革命。然而，相当一部分患者对免疫检查点抑制剂无反应或产生抗药性。因此，需要新的治疗方法或治疗方法的组合，可能会产生协同作用。有人提出，通过对髓系细胞进行再编程，诱导训练免疫可能会增加对免疫检查点抑制剂治疗的反应，使其向抗肿瘤表型转变。另一方面，免疫系统的激活也会带来潜在的肿瘤形成和免疫相关毒性增加的风险。我们报告了一例37岁的荷兰男性患有肥厚型神经内分泌癌并有肝转移的病例。这位患者面临不良结局的高风险，接受了编程细胞死亡蛋白1抑制剂尼伏单抗和具有训练免疫诱导剂性质的巴卡凡明活菌苗联合治疗。在免疫检查点抑制剂治疗方案的基础上，连续3个月间隔注射了3剂巴卡凡明活菌苗。在某个时间点，放射治疗被加入到治疗方案中。在这些治疗的联合使用中，患者出现了免疫介导的结肠炎，这迫使我们停止所有治疗。Bacillus Calmette-Guérin疫苗诱导了训练的免疫反应，并增强了单核细胞源性白细胞介素-6和白细胞介素-1β的产生能力。从第一次巴卡凡明活菌苗接种到最后一次接种3个月后，患者原发肿瘤只有轻微进展，转移病灶没有进展。在这项研究中，我们展示了将检查点抑制剂治疗与训练免疫诱导剂结合治疗应用于一位患有侵袭性神经内分泌肿瘤的患者是可行的。在编程细胞死亡蛋白1抑制剂治疗中，自身免疫副作用很常见，这被认为是结肠炎的最可能原因，尽管巴卡凡明活菌苗或放射治疗的叠加效应不能排除。患者在联合治疗期间只有轻微进展，但需要进行更大规模的研究，以全面探讨训练免疫诱导剂作为免疫检查点抑制剂治疗辅助剂的潜在益处。© 2023. BioMed Central Ltd., part of Springer Nature.

Immune checkpoint inhibitors have revolutionized therapy of advanced and metastatic cancers. However, a significant proportion of patients do not respond to immune checkpoint inhibitors or develop resistance. Therefore, novel therapies or combinations of therapies that may act synergistically are needed. It has been suggested that induction of trained immunity may increase the response to immune checkpoint inhibitor therapy, through reprogramming myeloid cells toward an antitumor phenotype. On the other hand, activation of the immune system also carries the risk of potentially sustaining tumorgenicity and increasing immune- related toxicity.We report the case of a 37-year-old Dutch male suffering from gastric neuroendocrine carcinoma with liver metastases and high risk for an unfavorable outcome, who was treated with a combination of programmed cell death protein 1 inhibitor nivolumab and the trained immunity-inducer Bacillus Calmette-Guérin vaccine as a salvage therapy. Three doses of BCG vaccine were administered at 3-month intervals, in conjunction with the immune checkpoint inhibitor regimen. At a certain point, radiation therapy was added to the treatment regimen. During the combination of these therapies, the patient developed immune-mediated colitis, which necessitated discontinuation of all treatments. Bacillus Calmette-Guérin vaccination induced a trained immune response with elevated monocyte-derived interleukin-6 and interleukin-1β production capacity. From the first vaccination with Bacillus Calmette-Guérin until 3 months after the last vaccination with Bacillus Calmette-Guérin, the patient displayed only mild progression of the primary tumor and no progression of the metastases.In this study, we show the feasibility to combine checkpoint inhibitor therapy with inducers of trained immunity in a patient with an aggressive neuroendocrine tumor. Autoimmune side effects are common under programmed cell death protein 1 inhibitor therapy, which was considered the most likely cause of colitis, although an additive effect of Bacillus Calmette-Guérin vaccination or radiotherapy cannot be excluded. The patient displayed only mild progression during the combination therapy, but larger studies are warranted to fully explore the potential benefit of trained immunity inducers as an adjuvant to immune checkpoint inhibitor therapy.© 2023. BioMed Central Ltd., part of Springer Nature.