The "Road of Hope" for precision immunotherapy for patients with lung squamous cancer in China Journal of Hematology & Oncology。

Title: Genomic landscape and its correlations with tumor mutational burden, PD-L1 expression, and immune cells in the chinese squamous cell carcinoma
Journal:
Tao Jiang, Jinpeng Shi, Zhengwei Dong, Likun Hou, Chao Zhao, Xuefei Li, Bei Bei Mao, Wei Zhu, Xianchao Guohui, Henghui Zhang, Ji He, Xiaoxia Chen, Chunxia Su, Sheng Xiang Ren, Chun Yan and Caicun Zhou
Published: 2019 07/12
DOI:
WeChat Link:
lung squamous cancer is one of the most common histological types of lung cancer. Unlike lung adenocarcinoma, treatment strategies for patients with lung squamous cancer have progressed very slowly over the past few decades, resulting in poor overall prognostication in such patients. Recently, immunotherapy with immunosuppressant PD-1/PD-L1 as the target has revolutionized the treatment strategies of the first, second and back lines of advanced lung squamous cancer. However, in clinical practice, the researchers found that PD-1/PD-L1 antibody single-drug treatment of unsuperviced patients with advanced lung squamous cancer, the efficiency is only about 20%, to explore effective efficacy prediction markers and reasonable combined immunotherapy strategy is the key problem to be solved in this field.
recently, researchers from Tongji University's Shanghai Lung Hospital published a study entitled "Genomic landscape and its correlations with tumouringal burden, PD-L1 expression and immune cells in china lung squamous carcinoma cell" in Journal of Hematology and Oncology.
the study calculated TMB for each sample (high TMB is defined as a 75% mine greater than the population) by retrospectively collecting 189 surgically removed lung squamous cancer samples and sequencing a deep total exon group. The expressions of CD8 plus tumor-soaked lymphocytes (TIL) and PD-L1 were tested by immunosomal chemical staining (IHC), with positive cutoff values defined as >5%. The results were as follows: 8 high-frequency mutation genes were found in the included samples, including TP53, KMT2C, NFE2L2, KEAP1, CDKN2A, PTEN, FBXW7 and PIK3CA. Among them, FGFR1 and PIX3CA amplification ratio of 19% and 11%, respectively. Except for smoking history, baseline characteristics were not associated with TMB expression. The amplification of FGFR1, PIK3CA or SOX2 is associated with higher TMB. The positive expression rates of PD-L1 and CD8 plus TIL were 24.3% and 78.8%, respectively. NFE2L2 mutations and PIK3CA amplification are associated with higher PD-L1 expressions.it is important to note that TMB expression is not associated with the positive rate of PD-L1 or CD8 plus TIL. TMB, CD8-plus TIL, and PD-L1 express a single indicator that does not predict prognosms, but TMB combined PD-L1 or CD8-plus TIL can predict prognosms well.Using PD-L1 and CD8-plus TIL expression levels to class divide the immuno-microencienties of lung squamous cancer into classic type IV (TME type I-IV), it was found that four TMEs had similar TMB levels, clinical pathological characteristics and prognosis, but they had different genetic variation characteristics, suggesting that the underlying cause of TME genotypes may be due to genetic mutations. These data provide rich evidence for the path of precision immunotherapy for patients with lung squamous cancer in China.。 To depict the genomic landscape of Chinese early-stage lung squamous cell carcinoma (LUSC) and investigate its correlation with tumor mutation burden (TMB), PD-L1 expression, and immune infiltrates.。 Whole-exome sequencing was performed on 189 surgically resected LUSC. TMB was defined as the sum of nonsynonymous single nucleotide and indel variants. CD8+tumor-infiltrating lymphocyte (TIL) density and PD-L1 expression were evaluated by immunohistochemistry. Six immune infiltrates were estimated using an online database.。 The median TMB was 9.43 mutations per megabase. Positive PD-L1 expression and CD8+ TILs density were identified in 24.3% and 78.8%. PIK3CA amplification was associated with significantly higher TMB (P = 0.036). Frequent genetic alterations had no impact on PD-L1 expression but PIK3CA amplification and KEAP1 mutation were independently associated with significantly lower CD8+ TIL density (P < 0.001, P = 0.005, respectively). Low TMB and high CD8+ TIL density were independently associated with longer disease-free survival (DFS) while none of them could individually predict the overall survival (OS). Combination of TMB and PD-L1 expression or TMB and CD8+ TIL density could stratify total populations into two groups with distinct prognosis. Classifying tumor-immune microenvironment based on PD-L1 expression and CD8+ TIL density showed discrepant genomic alterations but similar TMB, clinical features, and OS. Notably, patients with different smoking status had distinct prognostic factors.。 The combination of TMB, PD-L1 expression, immune infiltrates, and smoking status showed the feasibility to subgroup stratification in Chinese patients with early-stage LUSC, which might be helpful for future design of personalized immunotherapy trials in LUSC.
(Source: Science.com)