Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer
Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the re...
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2025-08-01
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| author | Hajime Matsuida Kosaku Mimura Shotaro Nakajima Katsuharu Saito Sohei Hayashishita Chiaki Takiguchi Azuma Nirei Tomohiro Kikuchi Hiroyuki Hanayama Hirokazu Okayama Motonobu Saito Tomoyuki Momma Zenichiro Saze Koji Kono |
| author_facet | Hajime Matsuida Kosaku Mimura Shotaro Nakajima Katsuharu Saito Sohei Hayashishita Chiaki Takiguchi Azuma Nirei Tomohiro Kikuchi Hiroyuki Hanayama Hirokazu Okayama Motonobu Saito Tomoyuki Momma Zenichiro Saze Koji Kono |
| author_sort | Hajime Matsuida |
| collection | DOAJ |
| description | Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. |
| format | Article |
| id | doaj-art-24f2fcd6c1924d56b53aed5c74d0a607 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-24f2fcd6c1924d56b53aed5c74d0a6072025-08-20T04:00:54ZengMDPI AGCells2073-44092025-08-011415121210.3390/cells14151212Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric CancerHajime Matsuida0Kosaku Mimura1Shotaro Nakajima2Katsuharu Saito3Sohei Hayashishita4Chiaki Takiguchi5Azuma Nirei6Tomohiro Kikuchi7Hiroyuki Hanayama8Hirokazu Okayama9Motonobu Saito10Tomoyuki Momma11Zenichiro Saze12Koji Kono13Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanBackground: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy.https://www.mdpi.com/2073-4409/14/15/1212anti-PD-1 therapygastric/gastroesophageal cancertumor resectiontumor immune microenvironmentHLA class ITGF-β |
| spellingShingle | Hajime Matsuida Kosaku Mimura Shotaro Nakajima Katsuharu Saito Sohei Hayashishita Chiaki Takiguchi Azuma Nirei Tomohiro Kikuchi Hiroyuki Hanayama Hirokazu Okayama Motonobu Saito Tomoyuki Momma Zenichiro Saze Koji Kono Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer Cells anti-PD-1 therapy gastric/gastroesophageal cancer tumor resection tumor immune microenvironment HLA class I TGF-β |
| title | Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer |
| title_full | Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer |
| title_fullStr | Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer |
| title_full_unstemmed | Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer |
| title_short | Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer |
| title_sort | residual tumor resection after anti pd 1 therapy a promising treatment strategy for overcoming immune evasive phenotype induced by anti pd 1 therapy in gastric cancer |
| topic | anti-PD-1 therapy gastric/gastroesophageal cancer tumor resection tumor immune microenvironment HLA class I TGF-β |
| url | https://www.mdpi.com/2073-4409/14/15/1212 |
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