Genomic Variations and Immune-Related Features of TMB, PD-L1 Expression and CD8+ T Cell Infiltration in Chinese Pulmonary Sarcomatoid Carcinoma

Abstract

Chenyue Zhang,1,* Zhenxiang Li,2,* Yanxiang Zhang,3 Chenglong Zhao,4 Hui Wang,5 Jiamao Lin,6 Cuicui Liu,7 Xiaohui Wang,8 Haiyong Wang9 1Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, 200032, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3Berry Oncology Corporation, Beijing, 102206, People’s Republic of China; 4Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, 250013, People’s Republic of China; 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 6Department of Traditional Chinese Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 7Department of Oncology, Linyi People’s Hospital, Linyi, 276000, People’s Republic of China; 8Research Service Office, Shandong Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 9Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyong Wang, Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Pulmonary sarcomatoid carcinoma (PSC) is a rare and distinct subtype of lung cancer characterized by its aggressiveness and dismal prognosis. However, genomic landscape and immune contexture have not been fully elucidated among PSC patients.Methods: In the present study, whole-exome-sequencing (WES) analyses were performed to depict genomic landscape of 38 independent PSC samples. Tumor mutation burden (TMB) was calculated with the total number of non-synonymous SNVs and indel variants per megabase of coding regions. PD-L1 expression and CD8+ T cell density were evaluated by immunohistochemistry in PSC samples. Their associations with genomic mutation were further assessed in genes with most frequent mutation. Overall survival (OS) of PSC patients with top mutated genes and high and low TMB, PD-L1 and CD8+ TIL expressions were further compared. Subgroup analyses of OS stratified by morphology and pathological type were conducted. Their correlation with TMB, PD-L1 and CD8+ T cell were further assessed.Results: We identified a cohort of genomic and somatic mutation in PSC patients. Subgroup patients with distinct clinicopathological features were found to harbor different genomic mutations and immunologic features. Besides, genomic profiles influenced outcomes, with SARS mutation associated with worsened prognosis.Conclusion: Through the mapping of genetic and immunologic landscape, we find the heterogeneity among the subgroups of PSC. Our findings may provide opportunities for therapeutic susceptibility among Chinese PSC patients.Keywords: pulmonary sarcomatoid carcinoma, mutational landscape, tumor mutational burden, programmed death ligand-1, CD8+ T cell

Keywords

• pulmonary sarcomatoid carcinoma
• mutational landscape
• tumor mutational burden
• programmed death ligand-1
• cd8+ t cell