Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1
Metrics: PDF 806 views | HTML 1303 views | ?
Emanuela Palmerini1, Claudio Agostinelli2, Piero Picci1, Stefano Pileri3,4, Teresa Marafioti5, Pier-Luigi Lollini6, Katia Scotlandi1, Alessandra Longhi1, Maria Serena Benassi1 and Stefano Ferrari1
1Chemotherapy Unit, IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy
2Haematopathology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy
3Haematopathology Unit, European Institute of Oncology, Milan, Italy
4Bologna University School of Medicine, Bologna, Italy
5University College London Cancer Institute, London, United Kingdom
6Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
Emanuela Palmerini, email: email@example.com
Keywords: osteosarcoma; PD-1; PD-L1; CD8; tumor microenvironment
Received: July 19, 2017 Accepted: November 15, 2017 Published: December 04, 2017
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis.
Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome.
Results: Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.
With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases.
Conclusions: Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.