• Kyoko Yamaguchi, Kenji Tsuchihashi, Kunihiro Tsuji, Yosuke Kito, Kenro Tanoue, Hirofumi Ohmura, Mamoru Ito, Taichi Isobe, Hiroshi Ariyama, Hitoshi Kusaba, Koichi Akashi, and Eishi Baba.
• Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
• Medicine (Baltimore). 2021 May 14; 100 (19): e25773.

RationaleAnti-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.Patient ConcernsIn the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment.DiagnosisAfter the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD.InterventionsMultiplex 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.OutcomesIn 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.LessonsThe 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.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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