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Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.


ABSTRACT: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis.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.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.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.

SUBMITTER: Palmerini E 

PROVIDER: S-EPMC5762363 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

Palmerini Emanuela E   Agostinelli Claudio C   Picci Piero P   Pileri Stefano S   Marafioti Teresa T   Lollini Pier-Luigi PL   Scotlandi Katia K   Longhi Alessandra A   Benassi Maria Serena MS   Ferrari Stefano S  

Oncotarget 20171204 67


<h4>Background</h4>We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis.<h4>Methods</h4>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 (m  ...[more]

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