The exploration of a novel predictor of immune-checkpoint inhibitor treatment efficacy in non-small cell lung carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tohoku University
• Principal Investigator: Saito-Koyama Ryoko (齋藤涼子) 東北大学, 医学系研究科, 非常勤講師 (30733349)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肺癌 / 扁平上皮癌 / 核異型 / PD-L1

Outline of Final Research Achievements

This study reveals that nuclear shape irregularity-related factors represented by aspect ratio, circularity, roundness and solidity, are significantly associated with PD-L1 expression in lung squamous cell carcinoma (LUSQ). In addition, LUSQ cases with high PD-L1 expression and severe nuclear atypia demonstrate C10orf71 and COL14A1 mutations more frequently. Practically, immunohistochemical expression level of PD-L1 in tumor is the most important methods for the determination of immune-checkpoint inhibitor (ICI) treatment. However, tiny specimens can be falsely evaluated as negative due to the heterogeneity of PD-L1 expression. When LUSQ tumor cells show severe nuclear shape irregularity, even if the first examination resulted in PD-L1 expression negativity, it may be worthy trying another examination using other specimens. Furthermore, examination about the function of COL14A1 and C10orf71 will be required in order to elucidate the significance of these extracted factors in LUSQ.

Free Research Field

Pulmonary pathology

Academic Significance and Societal Importance of the Research Achievements

核形不整の有無が免疫チェックポイント阻害薬の治療適応決定の一助となる可能性がある。また、C10orf71,COL14A1の肺ＳＣＣにおける機能を明らかにすることで治療の発展が期待される。例えば、治療感受性を低下させるC10orf71変異をターゲットとした治療の開発により、ICI+化学療法併用療法の治療効果を改善させることが可能になるかもしれない。