Journal Article

Neoadjuvant checkpoint blockade for cancer immunotherapy

Pardoll, Drew M., Taube, Janis M., Topalian, Suzanne L.

2020

Overview

Checkpoint blockade immunotherapy using antibodies that inhibit the programmed cell death 1 (PD-1) or cytotoxic T lymphocyte–associated protein 4 (CTLA-4) pathways has resulted in unprecedented clinical outcomes for certain cancers such as melanoma. Topalian et al. review advances in neoadjuvant (presurgical) immunotherapy as an important next step for enhancing the response of early-stage tumors to immune checkpoint blockade. They highlight the mechanistic rationale for neoadjuvant immunotherapy and recent neoadjuvant clinical trials based on anti–PD-1 or anti–PD-1 ligand 1 (anti–PD-L1) therapy. Pathological assessment criteria that may provide early on-treatment biomarkers to predict patient response are also discussed. Science , this issue p. eaax0182 Cancer immunotherapies that target the programmed cell death 1 (PD-1):programmed death-ligand 1 (PD-L1) immune checkpoint pathway have ushered in the modern oncology era. Drugs that block PD-1 or PD-L1 facilitate endogenous antitumor immunity and, because of their broad activity spectrum, have been regarded as a common denominator for cancer therapy. Nevertheless, many advanced tumors demonstrate de novo or acquired treatment resistance, and ongoing research efforts are focused on improving patient outcomes. Using anti–PD-1 or anti–PD-L1 treatment against earlier stages of cancer is hypothesized to be one such solution. This Review focuses on the development of neoadjuvant (presurgical) immunotherapy in the era of PD-1 pathway blockade, highlighting particular considerations for biological mechanisms, clinical trial design, and pathologic response assessments. Findings from neoadjuvant immunotherapy studies may reveal pathways, mechanisms, and molecules that can be cotargeted in new treatment combinations to increase anti–PD-1 and anti–PD-L1 efficacy.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Antibodies / Antigen (tumor-associated) / Antigen presentation / Antigens / Apoptosis / Assessments / B7-H1 Antigen - antagonists & inhibitors / Biomarkers / Breast cancer / Cancer / Cancer immunotherapy / Cancer therapies / Cell activation / Cell death / Cell proliferation / Chemotherapy / Clinical outcomes / Clinical trials / Clinical Trials as Topic / CTLA-4 protein / Cytotoxicity / Dendritic cells / Drugs / Exhaustion / Humans / Immune system / Immunity / Immunology / Immunosuppression / Immunosuppressive agents / Immunotherapy / Immunotherapy - methods / Ligands / Lung cancer / Lymph nodes / Lymphocytes / Lymphocytes T / Lymphoid tissue / Melanoma / Mortality / Narcotics / Neoadjuvant Therapy - methods / Neoplasms - immunology / Neoplasms - therapy / Oncology / Patients / PD-1 protein / PD-L1 protein / Priming / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Proteins / Regression / REVIEW SUMMARY / Surgery / T-Lymphocytes - immunology / Treatment resistance / Tumors