The tumor microenvironment (TME) can predict the efficacy of anti-PD-1/PD-L1 therapy in patients with advanced non-small cell lung cancer (NSCLC), according to a study published in the Journal of Thoracic Oncology.

Researchers investigated the association between the efficacy of anti-PD-1/PD-L1 therapy and types of TME based on PD-L1 expression and the presence of CD8-positive tumor-infiltrating lymphocytes (TILs).

The study included 228 patients with advanced NSCLC who were treated with anti-PD-1/PD-L1 therapy between 2015 and 2019.

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Patients were divided into 4 groups by TME type:  

  • The 73 patients with type I TME had high PD-L1 expression (tumor proportion score [TPS] ≥50%) and high TIL density (≥85/mm2).
  • The 70 patients with type II TME had low PD-L1 expression (TPS <50%) and low TIL density (<85/mm2).
  • The 37 patients with type III TME had high PD-L1 expression and low TIL density.
  • The 48 patients with type IV TME had low PD-L1 expression and high TIL density. 

Objective response rates (ORRs) and median progression-free survival (PFS) differed by TME, with the best outcomes observed in the type I and type IV groups.

The ORR was 64% for the type 1 group, 12% for the type 2 group, 24% for the type III group, and 41% for the type IV group. The median PFS was 14.5 months, 2.1 months, 3.6 months, and 10.8 months, respectively.

Among patients with high PD-L1 expression, those with type I TME had significantly better ORR (P <.001) and PFS (P <.001) than those with type III TME. 

When the researchers looked at the association between tumor histology and TME, they found that type Ⅰ tumors were predominantly associated with a pleomorphic and not otherwise specified histology. Type II and IV tumors were associated with large-cell neuroendocrine carcinoma, and adenocarcinoma was seen across TME types. 

The researchers concluded that TME types classified according to PD-L1 expression and TIL status predicted the clinical outcomes of anti-PD-1/PD-L1 therapy.

“Further research is needed to develop appropriate methods to assess TME and robust biomarkers related to TME classification and PD-L1 expression, and these can help to identify the best responders to anti-PD-1/PD-L1 therapy,” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Shirasawa M, Yoshida T, Shimoda Y, et al. Differential immune-related microenvironment determines PD-1/PD-L1 blockade efficacy in advanced non-small cell lung cancer patients. J Thorac Oncol. Published online August 19, 2021. doi:10.1016/j.jtho.2021.07.027