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Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy: The Galectin-3 Signature in NSCLCs

1
Department of Medical Oncology, Sant’Andrea University Hospital, 00189 Rome, Italy
2
Department of Molecular Medicine Sapienza University of Rome viale Regina Elena 324, 00161 Rome, Italy
3
Department of Oncology-Pathology Sant’Andrea University Hospital, via di Grottarossa 1035, 00189 Rome, Italy
4
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Hospital, S-17176 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1607; https://doi.org/10.3390/ijms20071607
Received: 3 March 2019 / Revised: 28 March 2019 / Accepted: 28 March 2019 / Published: 31 March 2019
(This article belongs to the Special Issue Galectins in Cancer and Translational Research 2.0)
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Abstract

Checkpoint inhibitor-based immunotherapy is opening a promising scenario in oncology, with objective responses registered in multiple cancer types. However, reliable predictive markers of tumor responsiveness are still lacking. These markers need to be urgently identified for a better selection of patients that can be candidates for immunotherapy. In this pilot study, a cohort of 34 consecutive patients bearing programmed death-ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC), treated with pembrolizumab, was considered. The retrospective immuno-phenotypic analysis performed on the original tumor biopsies allowed for the identification of a specific “galectin signature”, which strongly correlated with tumor responsiveness to anti PD-1 immunotherapy. We observed that the large majority of patients (about 90%) with high galectin-3 tumor expression (score 3+) showed an early and dramatic progression of the disease after three cycles of treatments. In contrast, all patients with negative or low/intermediate expression of galectin-3 in tumor cells showed an early and durable objective response to pembrolizumab, indicating galectin-3 as an interesting predictive marker of tumor responsiveness. The galectin-3 signature, at least in NSCLCs, promises a better selection of patient candidates for immunotherapy, reducing unnecessary treatment exposures and social costs. A large multicenter study is ongoing to validate this finding. View Full-Text
Keywords: galectin-3; non-small cell lung carcinoma; pembrolizumab; checkpoint inhibitors; predictive marker galectin-3; non-small cell lung carcinoma; pembrolizumab; checkpoint inhibitors; predictive marker
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Capalbo, C.; Scafetta, G.; Filetti, M.; Marchetti, P.; Bartolazzi, A. Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy: The Galectin-3 Signature in NSCLCs. Int. J. Mol. Sci. 2019, 20, 1607.

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