Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer
OX40 (CD134) is a co-stimulatory molecule mostly expressed on activated T lymphocytes. Previous reports have shown that OX40 can be an immuno-oncology target and a clinical biomarker for cancers of various organs. In this study, we collected formalin-fixed paraffin-embedded tumor samples from 124 pa...
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2021-01-01
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Online Access: | http://dx.doi.org/10.1080/2162402X.2021.1971430 |
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doaj-18254917a1194ec3b68c770c8b7a5de62021-09-20T12:43:26ZengTaylor & Francis GroupOncoImmunology2162-402X2021-01-0110110.1080/2162402X.2021.19714301971430Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancerHiroshi Yokouchi0Hiroshi Nishihara1Toshiyuki Harada2Toraji Amano3Takayuki Ohkuri4Shigeo Yamazaki5Hajime Kikuchi6Satoshi Oizumi7Hidetaka Uramoto8Fumihiro Tanaka9Masao Harada10Kenji Akie11Fumiko Sugaya12Yuka Fujita13Kei Takamura14Tetsuya Kojima15Mitsunori Higuchi16Osamu Honjo17Yoshinori Minami18Naomi Watanabe19Masaharu Nishimura20Hiroyuki Suzuki21Hirotoshi Dosaka-Akita22Hiroshi Isobe23Fukushima Medical UniversityHokkaido University Graduate School of MedicineJCHO Hokkaido HospitalHokkaido University HospitalAsahikawa Medical UniversityKeiyukai Sapporo HospitalHokkaido University School of MedicineNational Hospital Organization Hokkaido Cancer CenterUniversity of Occupational and Environmental HealthUniversity of Occupational and Environmental HealthNational Hospital Organization Hokkaido Cancer CenterSapporo City General HospitalTeine Keijinkai HospitalNational Hospital Organization Asahikawa Medical CenterObihiro-Kosei General HospitalKKR Sapporo Medical CenterFukushima Red Cross HospitalSapporo-Kosei General HospitalAsahikawa Medical UniversitySunagawa City Medical CenterHokkaido University School of MedicineFukushima Medical UniversityHokkaido University Graduate School of MedicineKKR Sapporo Medical CenterOX40 (CD134) is a co-stimulatory molecule mostly expressed on activated T lymphocytes. Previous reports have shown that OX40 can be an immuno-oncology target and a clinical biomarker for cancers of various organs. In this study, we collected formalin-fixed paraffin-embedded tumor samples from 124 patients with small-cell lung cancer (SCLC) who had undergone surgery. We analyzed the expression profiles of OX40 and other relevant molecules, such as CD4, CD8, and Foxp3, in tumor stroma and cancer nest using immunohistochemistry and investigated their association with survival. High infiltration of OX40+ lymphocytes (OX40high) in tumor stroma was positively associated with relapse-free survival (RFS) and overall survival (OS) compared with low infiltration of OX40+ lymphocytes (OX40low) (RFS, median, 26.0 months [95% confidence interval (CI), not reached (NR)–NR] vs 13.2 months [9.1–17.2], p = .024; OS, NR [95% CI, NR–NR] vs 29.8 months [21.3–38.2], p = .049). Multivariate analysis revealed that OX40high in tumor stroma was an independent indicator of prolonged RFS. Moreover, RFS of patients with OX40high/CD4high in tumor stroma was significantly longer than that of patients with OX40low/CD4low. The RFS of patients with tumor stroma with OX40high/CD8high was significantly longer than that of patients with tumor stroma with OX40low/CD8high, OX40high/CD8low, or OX40low/CD8low. These findings suggest that OX40+ lymphocytes in tumor stroma play a complementary role in regulating the relapse of early-stage SCLC. Reinforcing immunity by coordinating the recruitment of OX40+ lymphocytes with CD4+ and CD8+ T cells in tumor stroma may constitute a potential immunotherapeutic strategy for patients with SCLC.http://dx.doi.org/10.1080/2162402X.2021.1971430small-cell lung cancerox40cd4cd8survival |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroshi Yokouchi Hiroshi Nishihara Toshiyuki Harada Toraji Amano Takayuki Ohkuri Shigeo Yamazaki Hajime Kikuchi Satoshi Oizumi Hidetaka Uramoto Fumihiro Tanaka Masao Harada Kenji Akie Fumiko Sugaya Yuka Fujita Kei Takamura Tetsuya Kojima Mitsunori Higuchi Osamu Honjo Yoshinori Minami Naomi Watanabe Masaharu Nishimura Hiroyuki Suzuki Hirotoshi Dosaka-Akita Hiroshi Isobe |
spellingShingle |
Hiroshi Yokouchi Hiroshi Nishihara Toshiyuki Harada Toraji Amano Takayuki Ohkuri Shigeo Yamazaki Hajime Kikuchi Satoshi Oizumi Hidetaka Uramoto Fumihiro Tanaka Masao Harada Kenji Akie Fumiko Sugaya Yuka Fujita Kei Takamura Tetsuya Kojima Mitsunori Higuchi Osamu Honjo Yoshinori Minami Naomi Watanabe Masaharu Nishimura Hiroyuki Suzuki Hirotoshi Dosaka-Akita Hiroshi Isobe Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer OncoImmunology small-cell lung cancer ox40 cd4 cd8 survival |
author_facet |
Hiroshi Yokouchi Hiroshi Nishihara Toshiyuki Harada Toraji Amano Takayuki Ohkuri Shigeo Yamazaki Hajime Kikuchi Satoshi Oizumi Hidetaka Uramoto Fumihiro Tanaka Masao Harada Kenji Akie Fumiko Sugaya Yuka Fujita Kei Takamura Tetsuya Kojima Mitsunori Higuchi Osamu Honjo Yoshinori Minami Naomi Watanabe Masaharu Nishimura Hiroyuki Suzuki Hirotoshi Dosaka-Akita Hiroshi Isobe |
author_sort |
Hiroshi Yokouchi |
title |
Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer |
title_short |
Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer |
title_full |
Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer |
title_fullStr |
Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer |
title_full_unstemmed |
Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer |
title_sort |
prognostic significance of ox40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2021-01-01 |
description |
OX40 (CD134) is a co-stimulatory molecule mostly expressed on activated T lymphocytes. Previous reports have shown that OX40 can be an immuno-oncology target and a clinical biomarker for cancers of various organs. In this study, we collected formalin-fixed paraffin-embedded tumor samples from 124 patients with small-cell lung cancer (SCLC) who had undergone surgery. We analyzed the expression profiles of OX40 and other relevant molecules, such as CD4, CD8, and Foxp3, in tumor stroma and cancer nest using immunohistochemistry and investigated their association with survival. High infiltration of OX40+ lymphocytes (OX40high) in tumor stroma was positively associated with relapse-free survival (RFS) and overall survival (OS) compared with low infiltration of OX40+ lymphocytes (OX40low) (RFS, median, 26.0 months [95% confidence interval (CI), not reached (NR)–NR] vs 13.2 months [9.1–17.2], p = .024; OS, NR [95% CI, NR–NR] vs 29.8 months [21.3–38.2], p = .049). Multivariate analysis revealed that OX40high in tumor stroma was an independent indicator of prolonged RFS. Moreover, RFS of patients with OX40high/CD4high in tumor stroma was significantly longer than that of patients with OX40low/CD4low. The RFS of patients with tumor stroma with OX40high/CD8high was significantly longer than that of patients with tumor stroma with OX40low/CD8high, OX40high/CD8low, or OX40low/CD8low. These findings suggest that OX40+ lymphocytes in tumor stroma play a complementary role in regulating the relapse of early-stage SCLC. Reinforcing immunity by coordinating the recruitment of OX40+ lymphocytes with CD4+ and CD8+ T cells in tumor stroma may constitute a potential immunotherapeutic strategy for patients with SCLC. |
topic |
small-cell lung cancer ox40 cd4 cd8 survival |
url |
http://dx.doi.org/10.1080/2162402X.2021.1971430 |
work_keys_str_mv |
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