IMMUNE CHECKPOINT

INHIBITOR BIOMARKERS

• Programmed cell death ligand 1 (PDL1)

immunohistochemistry (IHC) uses various

scoring systems and cutoffs for particular

antibody clones to quantify PDL1 expression as

a predictive biomarker for specic FDA

lated by dividing the total number of PDL1

positive tumor cells by the total number of

tumor cells (

≥

1% positive cutoff).

- The combined positive score (CPS) is based

on dividing the number of PDL1 positive

cells (tumor cells, lymphocytes, macrophages)

by the number of tumor cells to predict

pembrolizumab efcacy in metastatic gastric

and gastroesophageal junctional carcinoma,

AND SELECT SOLID

TUMORS

Patricia C. Tsang, MD

Predictive biomarker testing plays a critical role

in targeted immuno-oncology, including the use

of immune checkpoint inhibitors (ICI) for various

solid tumors. Molecular advancements in cancers

bladder cancer and cervical cancer (Fig. 1). It

has the same cutoff of

≥

1%, using the 22C3

antibody clone.

- The PDL1 SP142 clone is an FDA approved

of metastatic NSCLC to atezolizumab. The

evaluation is based on either the proportion

of tumor area occupied by PDL1 expressing

tumors. While it is commonly tested by IHC,

assays based on PCR or next generation

sequencing (NGS) are available.

• High tumor mutational burden (TMB) may

also serve as a predictor of immunotherapy

response. TMB reects the number of somatic

mutations per megabase of tumor genomic

sequence. It can be determined by whole exome

sequencing (WES) or targeted sequencing of

CDx, which includes MSI

and TMB assessment, was approved as a

companion diagnostic for pembrolizumab with

a cutoff of

regardless of solid tumor type.

• NGS can simultaneously detect alterations of

multiple genes involved in breast cancers.

Clinically actionable genomic changes include

carry a lifetime cumulative risk of 60% and

55% to develop breast cancer, respectively.