Open AccessProminent PD-L1-positive M2 macrophage infiltration in gastric cancer with hyper-progression after anti-PD-1 therapy
Author(s) -
Kyoko Yamaguchi,
Kazufumi Tsuchihashi,
Kiichiro Tsuji,
Yosuke Kito,
Kimitoshi Tanoue,
Hirofumi Ohmura,
Mamoru Ito,
Taichi Isobe,
Hiroshi Ariyama,
Hitoshi Kusaba,
Koichi Akashi,
Eishi Baba
Publication year - 2021
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000025773
Subject(s) - medicine , nivolumab , antibody , metastasis , lymph node , immune system , cancer , immunohistochemistry , cytotoxic t cell , pd l1 , lymph , pathology , cancer research , immunology , immunotherapy , biochemistry , chemistry , in vitro
Rationale: 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. Patient concerns: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment. Diagnosis: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD. Interventions: 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. Outcomes: 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. Lessons: 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.