Table 2.

Examples of biomarkers that detect features of cancer cells, the tumor immune microenvironment, and systemic factors impacting immunotherapy response

Tumor tissue biomarkers		Patient-level/systemic immunity and tumor burden
Cancer cells	Tumor immune microenvironment
Pathology (eg, histology, grade)9	Checkpoint molecule expression (eg, PD-L1, Lag3)10 11	Patient demographics (age, sex, etc)
Targetable driver mutations (eg, Her2/Neu, EGFR)	Tumor-infiltrating immune cells, dendritic cells12	Tumor stage
Tumor mutational burden,11 13 Microsattelite Instability, MSI status	Interferon gamma signature	Metabolic studies/nutritional status (serum albumin, lactate, etc), microbiome14
Serum tumor markers (eg, CA19-9, CEA, CA-125, Prostate Specific Antigen, PSA)15	Radiomics8	Neutrophil lymphocyte ratio; Systemic Inflammatory Immune Index16
Circulating tumor DNA17	Digitized Imaging with machine learning outputs18	Lactate dehydrogenase
Targetable antigen expression (eg, CD19, CD20, mesothelin, Prostate specific membrane antigen, PSMA)	Single Cell RNA sequencing, multiomics19	Peripheral blood immune profiling (eg, T-cell repertoire,20 21 T-cell exhaustion)
		Stool microbiome 12

CA, cancer; CEA, carcinoembroyonic antigen; EGFR, epidermal growth factor receptor; Her2/Neu, human epidermal growth factor receptor 2/Neu protooncogene; LAG3, lymphocyte activation gene 3; LDH, Lactate dehydrogenase; MSI, Microsatellite instability; PD-L1, Programmed Death-Ligand 1; PSA, prostate specific antigen; PSMA, prostate specific membrane antigen; scRNA-seq, single cell ribonucleic acid sequencing.