Who Is Suitable for Immunotherapy? Understanding Biomarkers That Predict Treatment Response

The arrival of immune checkpoint inhibitors has given some patients with advanced cancer unprecedented long-term survival. However, overall, the response rate of immunotherapy alone is only about 20% to 30%, and the drugs are expensive and may cause unique immune-related side effects. Therefore, predicting who is most likely to benefit before treatment has become one of the most important clinical tasks—this is exactly the role of "biomarkers."

PD-L1: The Most Widely Used Marker

PD-L1 is a protein that cancer cells use to "put on the brakes" and suppress immune attacks. Through pathological slide staining, we can quantify the level of PD-L1 expression on tumor cells and immune cells. In many cancer types, the higher the PD-L1 expression, the better the response to immunotherapy. For example, in non-small cell lung cancer, patients with PD-L1 ≥ 50% may consider immunotherapy alone. But PD-L1 is not perfect: staining platforms and interpretation criteria vary, and some patients who are PD-L1 negative still respond.

MSI and TMB: Looking at the Tumor's "Mutation Burden"

Microsatellite instability-high (MSI-H) means the tumor's DNA repair mechanism is defective, leading to an accumulation of many mutations and thus many "neoantigens" that the immune system can recognize. MSI-H was the first marker approved as a "tumor-agnostic" indication for immunotherapy, and it is especially important in cancers such as colorectal cancer and endometrial cancer.

Tumor mutational burden (TMB) directly counts the number of mutations in the tumor genome. Tumors with high TMB are theoretically more easily recognized by the immune system, and some cancer types have incorporated TMB-H into treatment considerations. However, TMB testing requires next-generation sequencing, and the cutoff values for different testing platforms are still being standardized.

Integrated Interpretation and Future Trends

The current research trend is to integrate multiple markers—PD-L1, TMB, tumor-infiltrating lymphocytes, and even gut microbiota—to build more precise predictive models. For patients, the most practical advice is: discuss with your attending physician whether biomarker testing is needed, and understand how the test results may affect treatment options; if a specific marker is found, you may also meet the enrollment criteria for a particular clinical trial.