The following is the summary of “Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee” published in the December 2022 issue of Thoracic Oncology by Mino-Kenudson, et al. 

When treating advanced or metastatic lung cancer, immunotherapy, specifically immune checkpoint inhibitors (ICIs), has emerged as a mainstay of care. Their usage in neoadjuvant and adjuvant settings for early-stage malignancies has also increased. However, only a small percentage of patients significantly respond to ICIs. Protein expression of programmed death ligand 1 (PD-L1) by immunohistochemistry (IHC) has been used as a major predictive biomarker for immunotherapy, but it may not be as effective as it could be and has a ber of practical problems with the various companion diagnostic assays that have been approved. 

As a prognostic biomarker for ICIs, tumor mutational burden (TMB) also has several technical problems. Currently, there is active investigation into tumor- and host-immune-specific variables that have led to the identification of immunotherapy biomarkers that may improve response and prognosis prediction, especially in a multimodal setting. New information on PD-L1 immunohistochemistry (IHC) and tumor mutational burden (TMB) analysis, as well as evaluations of neoantigens, genetic and epigenetic signatures, immune microenvironment by IHC and transcriptomics, and the microbiome and pathologic response to neoadjuvant immunotherapies are all included in this review by the International Association for the Study of Lung Cancer Pathology Committee. 

The focus of this review is on the value of additional prognostic biomarkers beyond PD-L1 IHC and TMB, both of which have been shown to be rather useful.