Immuno-genomic analysis reveals eosinophilic feature and favorable prognosis of female non-smoking esophageal squamous cell carcinomas

• Published in: Cancer letters Vol. 581; p. 216499
• Main Authors: Okawa, Yuki, Sasagawa, Shota, Kato, Hiroaki, Johnson, Todd A., Nagaoka, Koji, Kobayashi, Yukari, Hayashi, Akimasa, Shibayama, Takahiro, Maejima, Kazuhiro, Tanaka, Hiroko, Miyano, Satoru, Shibahara, Junji, Nishizuka, Satoshi, Hirano, Satoshi, Seto, Yasuyuki, Iwaya, Takeshi, Kakimi, Kazuhiro, Yasuda, Takushi, Nakagawa, Hidewaki
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.01.2024
• Subjects: Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Eosinophils; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - genetics; Female; Genomics; Humans; Male; Mutational signature; Non-smoking female; Prognosis; Tumor Microenvironment; Esophageal squamous cell carcinoma; Non-smoking female; Tumor microenvironment; Mutational signature; Eosinophils
• ISSN: 0304-3835; 1872-7980; 1872-7980
• DOI: 10.1016/j.canlet.2023.216499

Most of esophageal squamous cell carcinoma (ESCC) develop in smoking males in Japan, but the genomic etiology and immunological characteristics of rare non-smoking female ECSS remain unclear. To elucidate the genomic and immunological features of ESCC in non-smoking females, we analyzed whole-genome or transcriptome sequencing data from 94 ESCCs, including 20 rare non-smoking female cases. In addition, 31,611 immune cells were extracted from four ESCC tissues and subject to single-cell RNA-seq. We compared their immuno-genomic and microbiome profiles between non-smoking female and smoking ESCCs. Non-smoking females showed much better prognosis. Whole-genome sequencing analysis showed no significant differences in driver genes or copy number alterations depending on smoking status. The mutational signatures specifically observed in non-smoking females ESCC could be attributed to aging. Immune profiling from RNA-seq revealed that ESCC in non-smoking females had high tumor microenvironment signatures and a high abundance of eosinophils with a favorable prognosis. Single-cell RNA-sequencing of intratumor immune cells revealed gender differences of eosinophils and their activation in female cases. ESCCs in non-smoking females have age-related mutational signatures and gender-specific tumor immune environment with eosinophils, which is likely to contribute to their favorable prognosis. •Risk factors for ESCC are often present in smoking males, but rare ESCCs in non-smoking females are recently present.•Immune-genomic analysis was performed on ESCC in non-smoking females, which show favorable prognosis.•Some mutational signatures specific to ESCCs in non-smoking females are likely to be age-related.•Single-cell analysis demonstrated that eosinophils and their activation in non-smoking female ESCCs.