The following is a summary of “Classification of Tumor Immune Microenvironment According to Programmed Death-Ligand 1 Expression and Immune Infiltration Predicts Response to Immunotherapy Plus Chemotherapy in Advanced Patients With NSCLC,” published in the July 2023 issue of the Thoracic Oncology by Sun et al.

According to adaptive immune resistance mechanisms, tumor immune microenvironment (TIME) is divided into four categories: PD-L1–negative and TIL–negative (type I); PD-L1–positive and TIL–positive (type II); PD-L1–negative and TIL–positive (type III); PD-L1–positive and TIL–negative (type IV). However, a large randomized controlled clinical trial has not validated the relationship between the TIME classification model and immunotherapy efficacy in patients with advanced NSCLC. Using RNA-sequencing and immunohistochemistry data from the ORIENT-11 study, researchers optimized the TIME classification model and assessed its ability to predict the efficacy of immunotherapy plus chemotherapy. 

PD-L1 mRNA expression and the immune score computed using the ESTIMATE method were the most accurate predictors of immunotherapy plus chemotherapy efficacy. Therefore, they were determined to be the optimal TIME classification system definition. Only the type II subpopulation with a high immune score and high PD-L1 mRNA expression was significantly associated with improved progression-free survival (PFS; hazard ratio = 0.12; 95% CI: 0.06–0.25; P<0.001) and overall survival (hazard ratio = 0.27; 95% CI: 0.13–0.52; P<0.001). 

In the combination group, the type II subpopulation had a significantly prolonged survival time, not even reaching the median PFS or overall survival. In contrast, the other three subpopulations were susceptible to having comparable PFS. There was no significant association between survival outcomes and TIME subtypes in the chemotherapy group. Only patients with high PD-L1 expression and high immune infiltration would benefit from chemotherapy plus immunotherapy as the initial treatment for advanced NSCLC. For patients without PD-L1 expression or immune infiltration, chemotherapy alone may be a preferable treatment option to avoid unnecessary toxicities and costs.

Source: sciencedirect.com/science/article/pii/S1556086423001946