Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab

• Main Authors: Toshiki Iwai, Masamichi Sugimoto, Namrata S. Patil, Daniel Bower, Miho Suzuki, Chie Kato, Keigo Yorozu, Mitsue Kurasawa, David S. Shames, Osamu Kondoh
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-07-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-021-93113-y

Abstract Anti-PD-L1 antibodies benefit many cancer patients, even those with “non-inflamed tumor”. Determining which patients will benefit remains an important clinical goal. In a non-inflamed tumor mouse model, we found that PD-L1 was highly expressed on antigen-presenting cells (APCs) especially on CD103+ CD11c+ dendritic cells in tumor-draining lymph nodes (dLNs), suppressing T-cell priming by APCs. In this model, anti-PD-L1 antibodies enhanced T-cell priming and increased CXCR3+ activated T-cells in dLNs, which was followed by the trafficking of T-cells to tumors in response to CXCR3 ligands. As predictive biomarker, each APCs-related gene expression (AP score) alone or T-cells trafficking-related chemokine gene expression (T score) alone were still less than perfect among the 17 mouse models examined. However a combining score of AP score and T score (AP/T score) precisely identified anti-PD-L1-sensitive tumors. In the phase 3 trial of atezolizumab vs docetaxel in advanced NSCLC patients (OAK), the AP/T score could identify atezolizumab-treated NSCLC patients who achieved significant improvement in overall survival. This biomarker concept would be a clinically valuable for prediction of anti-PD-L1 antibody efficacy.