The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Hiroaki Kanemura, MD, MPH, PhD; Toshihide Yokoyama, MD; Ryu Nakajima, MD, PhD; Atsushi Nakamura, MD, PhD; Hiroaki Kuroda, MD, PhD; Yoshitaka Kitamura, MD, PhD; Hiroyasu Shoda, MD, PhD; Nobuaki Mamesaya, MD, PhD; Yoshihiro Miyata, MD, PhD; Tatsuro Okamoto, MD, PhD; Kyoichi Okishio, MD, PhD; Masahide Oki, MD, PhD; Yuichi Sakairi, MD, PhD; Toyofumi Fengshi Chen-Yoshikawa, MD, PhD; Tadashi Aoki, MD; Tatsuo Ohira, MD, PhD; Isao Matsumoto, MD, PhD; Kiyonobu Ueno, MD, PhD; Takuro Miyazaki, MD, PhD; Haruhisa Matsuguma, MD, PhD; Hideoki Yokouchi, MD, PhD; Tomoyuki Otani, MD; Akihiko Ito, MD, PhD; Kazuko Sakai, PhD; Yasutaka Chiba, PhD; Kazuto Nishio, MD, PhD; Nobuyuki Yamamoto, MD, PhD; Isamu Okamoto, MD, PhD; Kazuhiko Nakagawa, MD, PhD; Masayuki Takeda, MD, PhD

JTO Clinical and Research Reports (Apr 2024)

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Hiroaki Kanemura, MD, MPH, PhD,
Toshihide Yokoyama, MD,
Ryu Nakajima, MD, PhD,
Atsushi Nakamura, MD, PhD,
Hiroaki Kuroda, MD, PhD,
Yoshitaka Kitamura, MD, PhD,
Hiroyasu Shoda, MD, PhD,
Nobuaki Mamesaya, MD, PhD,
Yoshihiro Miyata, MD, PhD,
Tatsuro Okamoto, MD, PhD,
Kyoichi Okishio, MD, PhD,
Masahide Oki, MD, PhD,
Yuichi Sakairi, MD, PhD,
Toyofumi Fengshi Chen-Yoshikawa, MD, PhD,
Tadashi Aoki, MD,
Tatsuo Ohira, MD, PhD,
Isao Matsumoto, MD, PhD,
Kiyonobu Ueno, MD, PhD,
Takuro Miyazaki, MD, PhD,
Haruhisa Matsuguma, MD, PhD,
Hideoki Yokouchi, MD, PhD,
Tomoyuki Otani, MD,
Akihiko Ito, MD, PhD,
Kazuko Sakai, PhD,
Yasutaka Chiba, PhD,
Kazuto Nishio, MD, PhD,
Nobuyuki Yamamoto, MD, PhD,
Isamu Okamoto, MD, PhD,
Kazuhiko Nakagawa, MD, PhD,
Masayuki Takeda, MD, PhD

Affiliations

Hiroaki Kanemura, MD, MPH, PhD: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Corresponding author. Address for correspondence: Hiroaki Kanemura, MD, MPH, PhD, Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Toshihide Yokoyama, MD: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan
Ryu Nakajima, MD, PhD: Department of General Thoracic Surgery, Osaka City General Hospital, Osaka, Japan
Atsushi Nakamura, MD, PhD: Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan
Hiroaki Kuroda, MD, PhD: Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
Yoshitaka Kitamura, MD, PhD: Division of Chest Surgery, Hyogo Cancer Center, Akashi, Japan
Hiroyasu Shoda, MD, PhD: Department of Respiratory Medicine, Hiroshima City Hiroshima Citizen Hospital, Hiroshima, Japan
Nobuaki Mamesaya, MD, PhD: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
Yoshihiro Miyata, MD, PhD: Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
Tatsuro Okamoto, MD, PhD: Department of Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan
Kyoichi Okishio, MD, PhD: Department of Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Osaka, Japan
Masahide Oki, MD, PhD: Department of Respiratory Medicine, NHO Nagoya Medical Center, Nagoya, Japan
Yuichi Sakairi, MD, PhD: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
Toyofumi Fengshi Chen-Yoshikawa, MD, PhD: Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
Tadashi Aoki, MD: Department of Chest Surgery, Niigata Cancer Center Hospital, Niigata, Japan
Tatsuo Ohira, MD, PhD: Department of Surgery, Tokyo Medical University, Tokyo, Japan
Isao Matsumoto, MD, PhD: Department of Thoracic Surgery, Kanazawa University, Kanazawa, Japan
Kiyonobu Ueno, MD, PhD: Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan
Takuro Miyazaki, MD, PhD: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Haruhisa Matsuguma, MD, PhD: Department of Thoracic Surgery, Tochigi Cancer Center, Utsunomiya, Japan
Hideoki Yokouchi, MD, PhD: Department of Surgery, Suita Municipal Hospital, Osaka, Japan
Tomoyuki Otani, MD: Department of Pathology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Akihiko Ito, MD, PhD: Department of Pathology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Kazuko Sakai, PhD: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Yasutaka Chiba, PhD: Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Japan
Kazuto Nishio, MD, PhD: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Nobuyuki Yamamoto, MD, PhD: Internal Medicine III, Wakayama Medical University, Wakayama, Japan
Isamu Okamoto, MD, PhD: Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Kazuhiko Nakagawa, MD, PhD: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Masayuki Takeda, MD, PhD: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Department of Cancer Genomics and Medical Oncology, Nara Medical University, Nara, Japan

Journal volume & issue: Vol. 5, no. 4
p. 100658

Abstract

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Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo–not reached; n = 39) and 23.7 months (95% CI: 14.5–43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29–0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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