Constructing a T-Cell Receptor-Related Gene Signature for Prognostic Stratification and Therapeutic Guidance in Head and Neck Squamous Cell Carcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Dec 9

PMID 38067199

Authors

Ye Lu

Zizhao Mai

Jiarong Zheng

Pei Lin

Yunfan Lin

Li Cui

Xinyuan Zhao

Affiliations

Soon will be listed here.

Abstract

Backgroud: The stratification of head and neck squamous cell carcinoma (HNSCC) patients based on prognostic differences is critical for therapeutic guidance. This study was designed to construct a predictive signature derived from T-cell receptor-related genes (TCRRGs) to forecast the clinical outcomes in HNSCC.

Methods: We sourced gene expression profiles from The Cancer Genome Atlas (TCGA) HNSCC dataset, GSE41613, and GSE65858 datasets. Utilizing consensus clustering analysis, we identified two distinct HNSCC clusters according to TCRRG expression. A TCRRG-based signature was subsequently developed and validated across diverse independent HNSCC cohorts. Moreover, we established a nomogram model based on TCRRGs. We further explored differences in immune landscapes between high- and low-risk groups.

Results: The TCGA HNSCC dataset was stratified into two clusters, displaying marked variations in both overall survival (OS) and immune cell infiltration. Furthermore, we developed a robust prognostic signature based on TCRRG utilizing the TCGA HNSCC train cohort, and its prognostic efficacy was validated in the TCGA HNSCC test cohort, GSE41613, and GSE65858. Importantly, the high-risk group was characterized by a suppressive immune microenvironment, in contrast to the low-risk group. Our study successfully developed a robust TCRRG-based signature that accurately predicts clinical outcomes in HNSCC, offering valuable strategies for improved treatments.

References

Behrens A, Sabapathy K, GRAEF I, Cleary M, Crabtree G, Wagner E . Jun N-terminal kinase 2 modulates thymocyte apoptosis and T cell activation through c-Jun and nuclear factor of activated T cell (NF-AT). Proc Natl Acad Sci U S A. 2001; 98(4):1769-74. PMC: 29332. DOI: 10.1073/pnas.98.4.1769. View

Boyer M, Sendur M, Rodriguez-Abreu D, Park K, Lee D, Cicin I . Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021; 39(21):2327-2338. DOI: 10.1200/JCO.20.03579. View

Chan J, Zhen G, Agrawal N . The role of tumor DNA as a diagnostic tool for head and neck squamous cell carcinoma. Semin Cancer Biol. 2018; 55:1-7. DOI: 10.1016/j.semcancer.2018.07.008. View

Wu M, Huang Q, Xie Y, Wu X, Ma H, Zhang Y . Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation. J Hematol Oncol. 2022; 15(1):24. PMC: 8917703. DOI: 10.1186/s13045-022-01242-2. View

Chu X, Tian W, Wang Z, Zhang J, Zhou R . Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials. Mol Cancer. 2023; 22(1):93. PMC: 10249258. DOI: 10.1186/s12943-023-01800-3. View

Foy J, Karabajakian A, Ortiz-Cuaran S, Boussageon M, Michon L, Bouaoud J . Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients. Eur J Cancer. 2022; 174:287-298. DOI: 10.1016/j.ejca.2022.06.034. View

Triantafyllou E, Gudd C, Mawhin M, Husbyn H, Trovato F, Siggins M . PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury. J Clin Invest. 2020; 131(4). PMC: 7880414. DOI: 10.1172/JCI140196. View

Molling J, Langius J, Langendijk J, Leemans C, Bontkes H, van der Vliet H . Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol. 2007; 25(7):862-8. DOI: 10.1200/JCO.2006.08.5787. View

Klebanoff C, Rosenberg S, Restifo N . Prospects for gene-engineered T cell immunotherapy for solid cancers. Nat Med. 2016; 22(1):26-36. PMC: 6295670. DOI: 10.1038/nm.4015. View

10.

Hammouda M, Ford A, Liu Y, Zhang J . The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer. Cells. 2020; 9(4). PMC: 7226813. DOI: 10.3390/cells9040857. View

11.

Pages G, Guerin S, Grall D, Bonino F, Smith A, Anjuere F . Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science. 1999; 286(5443):1374-7. DOI: 10.1126/science.286.5443.1374. View

12.

Bendix I, Pfueller C, Leuenberger T, Glezeva N, Siffrin V, Muller Y . MAPK3 deficiency drives autoimmunity via DC arming. Eur J Immunol. 2010; 40(5):1486-95. DOI: 10.1002/eji.200939930. View

13.

Marletta S, Fusco N, Munari E, Luchini C, Cimadamore A, Brunelli M . Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems. J Pers Med. 2022; 12(7). PMC: 9321150. DOI: 10.3390/jpm12071073. View

14.

Fischer A, Katayama C, Pages G, Pouyssegur J, Hedrick S . The role of erk1 and erk2 in multiple stages of T cell development. Immunity. 2005; 23(4):431-43. DOI: 10.1016/j.immuni.2005.08.013. View

15.

Bromley S, Iaboni A, Davis S, Whitty A, Green J, Shaw A . The immunological synapse and CD28-CD80 interactions. Nat Immunol. 2001; 2(12):1159-66. DOI: 10.1038/ni737. View

16.

Cui L, Chen H, Zhao X . The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma. Diagnostics (Basel). 2020; 10(9). PMC: 7555784. DOI: 10.3390/diagnostics10090689. View

17.

Kingwell K . T cell receptor therapeutics hit the immuno-oncology stage. Nat Rev Drug Discov. 2022; 21(5):321-323. DOI: 10.1038/d41573-022-00073-7. View

18.

Cramer J, Burtness B, Le Q, Ferris R . The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019; 16(11):669-683. DOI: 10.1038/s41571-019-0227-z. View

19.

Zhao X, Chen H, Qiu Y, Cui L . FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1. Int J Oral Sci. 2022; 14(1):25. PMC: 9091245. DOI: 10.1038/s41368-022-00174-4. View

20.

Wu M, Buchanan J, Luik R, Lewis R . Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J Cell Biol. 2006; 174(6):803-13. PMC: 2064335. DOI: 10.1083/jcb.200604014. View