Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer
IntroductionThe efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patie...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1193533/full |
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| author | Iori Motoo Takayuki Ando Takeru Hamashima Shinya Kajiura Miho Sakumura Yuko Ueda Aiko Murayama Kohei Ogawa Kenichiro Tsukada Akira Ueda Nobuhiro Suzuki Naokatsu Nakada Koji Nakashima Ayumu Hosokawa Ayumu Hosokawa Ichiro Yasuda |
| author_facet | Iori Motoo Takayuki Ando Takeru Hamashima Shinya Kajiura Miho Sakumura Yuko Ueda Aiko Murayama Kohei Ogawa Kenichiro Tsukada Akira Ueda Nobuhiro Suzuki Naokatsu Nakada Koji Nakashima Ayumu Hosokawa Ayumu Hosokawa Ichiro Yasuda |
| author_sort | Iori Motoo |
| collection | DOAJ |
| description | IntroductionThe efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells.MethodsPatients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared.ResultsAmong 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32–0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00–2.87) and systemic progression (HR, 3.09, 95%CI, 1.95–4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04–8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different.ConclusionThe new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells. |
| first_indexed | 2024-03-11T23:57:29Z |
| format | Article |
| id | doaj.art-b48a1838f6a541f9b2469be5d9906eeb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-11T23:57:29Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b48a1838f6a541f9b2469be5d9906eeb2023-09-18T08:00:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.11935331193533Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancerIori Motoo0Takayuki Ando1Takeru Hamashima2Shinya Kajiura3Miho Sakumura4Yuko Ueda5Aiko Murayama6Kohei Ogawa7Kenichiro Tsukada8Akira Ueda9Nobuhiro Suzuki10Naokatsu Nakada11Koji Nakashima12Ayumu Hosokawa13Ayumu Hosokawa14Ichiro Yasuda15Third Department of Internal Medicine, University of Toyama, Toyama, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanDepartment of Pathology, University of Toyama, Toyama, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanDepartment of Gastroenterology, Toyama Prefectural Central Hospital, Toyama, JapanDepartment of Gastroenterology, Kouseiren Takaoka Hospital, Takaoka, JapanDepartment of Medical Oncology, Toyama Red Cross Hospital, Toyama, JapanDepartment of Gastroenterology, Jouetsu Sogo Hospital, Jouetsu, JapanDepartment of Gastroenterology, Itoigawa Sogo Hospital, Itoigawa, JapanDepartment of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanDepartment of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, JapanThird Department of Internal Medicine, University of Toyama, Toyama, JapanIntroductionThe efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells.MethodsPatients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared.ResultsAmong 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32–0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00–2.87) and systemic progression (HR, 3.09, 95%CI, 1.95–4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04–8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different.ConclusionThe new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.https://www.frontiersin.org/articles/10.3389/fonc.2023.1193533/fullgastric cancerimmune checkpoint inhibitorprogression patternliver metastasistumor-infiltrating lymphocytes |
| spellingShingle | Iori Motoo Takayuki Ando Takeru Hamashima Shinya Kajiura Miho Sakumura Yuko Ueda Aiko Murayama Kohei Ogawa Kenichiro Tsukada Akira Ueda Nobuhiro Suzuki Naokatsu Nakada Koji Nakashima Ayumu Hosokawa Ayumu Hosokawa Ichiro Yasuda Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer Frontiers in Oncology gastric cancer immune checkpoint inhibitor progression pattern liver metastasis tumor-infiltrating lymphocytes |
| title | Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer |
| title_full | Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer |
| title_fullStr | Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer |
| title_full_unstemmed | Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer |
| title_short | Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer |
| title_sort | liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer |
| topic | gastric cancer immune checkpoint inhibitor progression pattern liver metastasis tumor-infiltrating lymphocytes |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1193533/full |
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