Neoadjuvant Chemoradiotherapy Upregulates the Immunogenicity of Cold to Hot Tumors in Esophageal Cancer Patients

Yushi Nagaki, MD, PhD; Satoru Motoyama, MD, PhD; Yusuke Sato, MD, PhD; Akiyuki Wakita, MD, PhD; Hiromu Fujita, MD, PhD; Kohei Kemuriyama, MD; Ryohei Sasamori, MD; Shu Nozaki, MD; Kyoko Nomura, MD, PhD; Yoshihiro Minamiya, MD, PhD

doi:10.1097/AS9.0000000000000385

Annals of Surgery Open (Mar 2024)

Neoadjuvant Chemoradiotherapy Upregulates the Immunogenicity of Cold to Hot Tumors in Esophageal Cancer Patients

Yushi Nagaki, MD, PhD,
Satoru Motoyama, MD, PhD,
Yusuke Sato, MD, PhD,
Akiyuki Wakita, MD, PhD,
Hiromu Fujita, MD, PhD,
Kohei Kemuriyama, MD,
Ryohei Sasamori, MD,
Shu Nozaki, MD,
Kyoko Nomura, MD, PhD,
Yoshihiro Minamiya, MD, PhD

Affiliations

Yushi Nagaki, MD, PhD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Satoru Motoyama, MD, PhD: ‡ Department of Gastrointestinal Surgery, Japanese Red Cross Akita Hospital, Akita, Japan
Yusuke Sato, MD, PhD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Akiyuki Wakita, MD, PhD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Hiromu Fujita, MD, PhD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Kohei Kemuriyama, MD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Ryohei Sasamori, MD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Shu Nozaki, MD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan
Kyoko Nomura, MD, PhD: § Department of Health Environmental Science and Public Health, Akita University Graduate School of Medicine, Akita, Japan.
Yoshihiro Minamiya, MD, PhD: * From the Division of Esophageal Surgery, Akita University Hospital, Akita, Japan

DOI: https://doi.org/10.1097/AS9.0000000000000385
Journal volume & issue: Vol. 5, no. 1
p. e385

Abstract

Read online

Objective:. To test the hypothesis that neoadjuvant chemoradiotherapy (NACRT) is more effective against hot esophageal squamous cell carcinoma (ESCC) and that it may upregulate tumor immunogenicity. Background:. There have been several recent reports showing the efficacy of immune check-point inhibitors (ICIs) against esophageal cancer, especially immunologically hot tumors. In addition, several studies have suggested that chemotherapy and radiotherapy may convert cold tumors to hot tumors. Methods:. Of 105 ESCC patients who underwent surgery after NACRT between 2010 and 2018 at our hospital, 99 whose biopsy tissue samples were obtained were enrolled. Based on immunohistochemical analysis, tumors that were FOXA1 (+) and/or EYA2 (+) were defined as hot tumors, others were cold tumors. We then investigated the association between tumor immunogenicity and clinicopathological features. Results:. The 29 patients with hot tumors before NACRT had a significantly better 5-year disease-specific survival (DSS) rate than the remaining 70 patients with cold tumors (85% vs 64%; P = 0.036). In a multivariate analysis, tumor immunogenicity was a significant independent predictor of DSS. Of 68 patients without a pathological complete response (non-pCR) in their primary tumor, 51 (75%) had hot tumors after NACRT. Moreover, 75% (36/48) of tumors that were cold before NACRT were converted to hot tumors after NACRT. Conclusions:. Patients with hot ESCC tumors treated with NACRT plus esophagectomy had a better prognosis than those with cold tumors. NACRT upregulated cold tumor immunogenicity to hot tumors, suggesting NACRT may increase the sensitivity of ESCC to adjuvant ICIs.

Published in Annals of Surgery Open

ISSN: 2691-3593 (Online)
Publisher: Wolters Kluwer Health
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: https://journals.lww.com/aosopen/pages/default.aspx

About the journal