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Abstract：
BACKGROUND: Anti-PD-1 antibody is the standard therapy for treatment-resistant gastric cancer, but only a limited number of patients respond. Additionally, cases of hyper-progressive disease (HPD) in which tumor growth accelerates after anti-PD-1 antibody administration have been reported; however, the biological mechanism has not been elucidated.
UNASSIGNED: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment.
METHODS: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD.
METHODS: Multiplex immunohistochemistry was used to examine immune cells infiltrating in the primary tumor and in liver metastasis which were obtained before nivolumab treatment, and in lymph node metastasis which presented with HPD after nivolumab therapy.
RESULTS: In the primary tumor, helper T (Th) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and PD-L1-negative macrophages were observed. On the other hand, in metastatic lymph nodes presenting with HPD, PD-L1-positive macrophages prominently increased, while Treg cells, CTLs, and Th cells decreased. PD-L1 expression was not observed in gastric cancer cells among the three specimens.
CONCLUSIONS: The findings suggest the possibility that PD-L1-positive M2 macrophage might contribute to acceleration of tumor growth with anti-PD-1 therapy in the present case.
UNASSIGNED: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment.
METHODS: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD.
METHODS: Multiplex immunohistochemistry was used to examine immune cells infiltrating in the primary tumor and in liver metastasis which were obtained before nivolumab treatment, and in lymph node metastasis which presented with HPD after nivolumab therapy.
RESULTS: In the primary tumor, helper T (Th) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and PD-L1-negative macrophages were observed. On the other hand, in metastatic lymph nodes presenting with HPD, PD-L1-positive macrophages prominently increased, while Treg cells, CTLs, and Th cells decreased. PD-L1 expression was not observed in gastric cancer cells among the three specimens.
CONCLUSIONS: The findings suggest the possibility that PD-L1-positive M2 macrophage might contribute to acceleration of tumor growth with anti-PD-1 therapy in the present case.
摘要：
背景：抗PD-1抗体是治疗耐药胃癌的标准疗法，但只有有限数量的患者有反应。此外,已经报道了抗PD-1抗体给药后肿瘤生长加速的超进行性疾病（HPD）病例；然而，生物学机制尚未阐明。
■在目前的情况下，转移性胃癌用抗PD-1抗体治疗，Nivolumab,作为三线治疗。
方法：开始纳武单抗治疗后，观察到快速扩大的主动脉旁淋巴结导致HPD的诊断。
方法：多重免疫组织化学用于检查在纳武单抗治疗前获得的原发肿瘤和肝转移中浸润的免疫细胞，以及纳武单抗治疗后出现HPD的淋巴结转移。
结果：在原发肿瘤中，辅助性T（Th）细胞，细胞毒性T淋巴细胞（CTL），调节性T(Treg)细胞,观察到PD-L1阴性巨噬细胞。另一方面,出现HPD的转移性淋巴结，PD-L1阳性巨噬细胞显著增加，而Treg细胞,CTL,Th细胞减少。3例胃癌细胞中均未观察到PD-L1表达。
结论：研究结果表明，在本病例中，PD-L1阳性M2巨噬细胞可能有助于抗PD-1治疗加速肿瘤生长。
■在目前的情况下，转移性胃癌用抗PD-1抗体治疗，Nivolumab,作为三线治疗。
方法：开始纳武单抗治疗后，观察到快速扩大的主动脉旁淋巴结导致HPD的诊断。
方法：多重免疫组织化学用于检查在纳武单抗治疗前获得的原发肿瘤和肝转移中浸润的免疫细胞，以及纳武单抗治疗后出现HPD的淋巴结转移。
结果：在原发肿瘤中，辅助性T（Th）细胞，细胞毒性T淋巴细胞（CTL），调节性T(Treg)细胞,观察到PD-L1阴性巨噬细胞。另一方面,出现HPD的转移性淋巴结，PD-L1阳性巨噬细胞显著增加，而Treg细胞,CTL,Th细胞减少。3例胃癌细胞中均未观察到PD-L1表达。
结论：研究结果表明，在本病例中，PD-L1阳性M2巨噬细胞可能有助于抗PD-1治疗加速肿瘤生长。
