Neoadjuvant Immunotherapy: A Promising New Standard of Care

Abstract

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various malignancies, with preclinical studies showing improved immune responses in the preoperative setting. FDA-approved neoadjuvant-immunotherapy-based approaches include triple-negative breast cancer and early non-small cell lung cancer on the basis of improvement in pathological response and event free survival. Nevertheless, current trials have only shown benefits in a fraction of patients. It is therefore crucial to identify predictive biomarkers to improve patient selection for such approaches. This review aims to provide an overview of potential biomarkers of neoadjuvant immunotherapy in early triple-negative breast cancer, bladder cancer, melanoma, non-small cell lung cancer, colorectal cancer and gastric cancer. By the extrapolation of the metastatic setting, we explore known predictive biomarkers, i.e., PD-L1, mismatch repair deficiency and tumour mutational burden, as well as potential early-disease-specific biomarkers. We also discuss the challenges of identifying reliable biomarkers and the need for standardized protocols and guidelines for their validation and clinical implementation.

Keywords: NSCLC; gastric cancer; immunotherapy; melanoma; neoadjuvant; predictive biomarkers; urothelial carcinoma.

Figure 1

Potential predictors of response to neoadjuvant immunotherapy. PD-1 or PD-L1 expression may influence sensitivity to immunotherapy. The tumour microenvironment, including CD8 T-infiltrating lymphocytes (sensitivity) and regulatory T cells (resistance), may influence the effect of immunotherapy. Antigenic diversity, as seen in high tumour mutation burden or microsatellite instability, may influence sensitivity to immunotherapy. The T cell receptor repertoire or diversity may increase the efficacy of immunotherapy. PD: programmed death, T-reg: regulatory T cell, TCR: T cell receptor, MHC: major histocompatibility complex and CD8: cytotoxic T lymphocytes.