Yusuke Kono1, Hiroaki Saito2, Wataru Miyauchi1, Shota Shimizu1, Yuki Murakami3, Yuji Shishido1, Kozo Miyatani1, Tomoyuki Matsunaga1, Yoji Fukumoto1, Yuji Nakayama4, Chiye Sakurai5, Kiyotaka Hatsuzawa5, Yoshiyuki Fujiwara1. 1. Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan. 2. Department of Surgery, Japanese Red Cross Tottori Hospital, 117 Shotoku-cho, Tottori, 680-8517, Japan. sai10@tottori-med.jrc.or.jp. 3. Department of Surgery, Japanese Red Cross Tottori Hospital, 117 Shotoku-cho, Tottori, 680-8517, Japan. 4. Division of Radioisotope Science, Research, Initiative Center, Organization for Research Initiative and Promotion, Tottori University, 86 Nishi-cho, Yonago City, Tottori, 683-8503, Japan. 5. Division of Molecular Biology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
Abstract
BACKGROUND: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients. METHODS: The frequency of PD-1+ macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1+ macrophages, clinicopathological characteristics, and prognosis in GC patients (n = 102). RESULTS: The frequency of PD-1+ macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1+ macrophages was severely impaired compared with that of PD-1- macrophages. The 5-year disease-specific survival rates in patients with PD-1+ macrophageLow (the frequency of PD-1+ macrophages; < 0.85%) and those with PD-1+ macrophageHigh (the frequency of PD-1+ macrophages; ≥ 0.85%) were 85.9 and 65.8%, respectively (P = 0.008). Finally, multivariate analysis showed the frequency of PD-1+ macrophage to be an independent prognostic factor. CONCLUSIONS: The function of PD-1+ macrophage was severely impaired and increased frequency of PD-1+ macrophage worsened the prognosis of GC patients. PD-1-PD-L1 therapies may function through a direct effect on macrophages in GC.
BACKGROUND: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients. METHODS: The frequency of PD-1+ macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1+ macrophages, clinicopathological characteristics, and prognosis in GCpatients (n = 102). RESULTS: The frequency of PD-1+ macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1+ macrophages was severely impaired compared with that of PD-1- macrophages. The 5-year disease-specific survival rates in patients with PD-1+ macrophageLow (the frequency of PD-1+ macrophages; < 0.85%) and those with PD-1+ macrophageHigh (the frequency of PD-1+ macrophages; ≥ 0.85%) were 85.9 and 65.8%, respectively (P = 0.008). Finally, multivariate analysis showed the frequency of PD-1+ macrophage to be an independent prognostic factor. CONCLUSIONS: The function of PD-1+ macrophage was severely impaired and increased frequency of PD-1+ macrophage worsened the prognosis of GCpatients. PD-1-PD-L1 therapies may function through a direct effect on macrophages in GC.
Authors: Haoran Zha; Ying Jiang; Xi Wang; Jin Shang; Ning Wang; Lei Yu; Wei Zhao; Zhihua Li; Juan An; Xiaochun Zhang; Huoming Chen; Bo Zhu; Zhaoxia Li Journal: J Immunother Cancer Date: 2021-02 Impact factor: 13.751
Authors: Jens von der Grün; Ria Winkelmann; Iris Burck; Daniel Martin; Franz Rödel; Peter Johannes Wild; Katrin Bankov; Andreas Weigert; Ivan-Maximiliano Kur; Christian Brandts; Natalie Filmann; Christian Issing; Philipp Thönissen; Anna Maria Tanneberger; Claus Rödel; Shahram Ghanaati; Panagiotis Balermpas Journal: Front Oncol Date: 2022-03-24 Impact factor: 6.244