TY - JOUR
T1 - Prognostic significance of OX40+ lymphocytes in tumor stroma of surgically resected small-cell lung cancer
AU - Yokouchi, Hiroshi
AU - Nishihara, Hiroshi
AU - Harada, Toshiyuki
AU - Amano, Toraji
AU - Ohkuri, Takayuki
AU - Yamazaki, Shigeo
AU - Kikuchi, Hajime
AU - Oizumi, Satoshi
AU - Uramoto, Hidetaka
AU - Tanaka, Fumihiro
AU - Harada, Masao
AU - Akie, Kenji
AU - Sugaya, Fumiko
AU - Fujita, Yuka
AU - Takamura, Kei
AU - Kojima, Tetsuya
AU - Higuchi, Mitsunori
AU - Honjo, Osamu
AU - Minami, Yoshinori
AU - Watanabe, Naomi
AU - Nishimura, Masaharu
AU - Suzuki, Hiroyuki
AU - Dosaka-Akita, Hirotoshi
AU - Isobe, Hiroshi
N1 - Funding Information:
The analysis in this work was supported by research funding from the Department of Translational Pathology, Hokkaido University Graduate School of Medicine; the Center for Respiratory Diseases, JCHO Hokkaido Hospital; the Department of Pulmonary Medicine, Fukushima Medical University; and the Department of Respiratory Medicine, Hokkaido Cancer Center. The study sponsors did not have any role in the study design, data collection, interpretation of data, writing of the report, and decision to submit this paper for publication. Assistance in English proofreading was paid for by the Department of Respiratory Medicine, Hokkaido Cancer Center. The authors thank all the patients and families who provided written consent and participated in this study. The authors also thank Dr. Yasuhiro Chikaishi (University of Occupational Environmental Health) for participating in this study and collecting data for use in this study.
Funding Information:
Dr. Masao Harada received grants from AstraZeneca and Chugai Pharmaceutical.
Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - CD4
KW - CD8
KW - OX40
KW - Small-cell lung cancer
KW - survival
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U2 - 10.1080/2162402X.2021.1971430
DO - 10.1080/2162402X.2021.1971430
M3 - Article
C2 - 34552823
AN - SCOPUS:85115247622
SN - 2162-4011
VL - 10
JO - OncoImmunology
JF - OncoImmunology
IS - 1
M1 - 1971430
ER -
