Intratumoral Heterogeneity Assessment of the Extracellular Bone Matrix and Immune Microenvironment in Osteosarcoma Using Digital Imaging to Predict Therapeutic Response.

Autor:	Gomez-Mascard A; Department of Pathology, CHU, IUCT-Oncopole, University of Toulouse, Eq19. ONCOSARC CRCT, UMR 1037 Inserm/UT3, ERL 5294 CNRS, Toulouse, France. Electronic address: GOMEZ.Anne@chu-toulouse.fr., Van Acker N; Department of Pathology, CHU, IUCT-Oncopole, University of Toulouse, Eq19. ONCOSARC CRCT, UMR 1037 Inserm/UT3, ERL 5294 CNRS, Toulouse, France; Department of Pathology, CHU, Imag'IN Platform, IUCT-Oncopole, Toulouse, France., Cases G; Department of Pathology, CHU, IUCT-Oncopole, University of Toulouse, Eq19. ONCOSARC CRCT, UMR 1037 Inserm/UT3, ERL 5294 CNRS, Toulouse, France., Mancini A; Institut de Mécanique des Fluides de Toulouse, UMR 5502 CNRS, INPT, University of Toulouse, Toulouse, France., Galanou S; Department of Pathology, CHU, IUCT-Oncopole, University of Toulouse, Eq19. ONCOSARC CRCT, UMR 1037 Inserm/UT3, ERL 5294 CNRS, Toulouse, France., Frenois FX; Department of Pathology, CHU, IUCT-Oncopole, University of Toulouse, Eq19. ONCOSARC CRCT, UMR 1037 Inserm/UT3, ERL 5294 CNRS, Toulouse, France; Department of Pathology, CHU, Imag'IN Platform, IUCT-Oncopole, Toulouse, France., Brousset P; Department of Pathology, CHU, IUCT-Oncopole, University of Toulouse, Eq19. ONCOSARC CRCT, UMR 1037 Inserm/UT3, ERL 5294 CNRS, Toulouse, France; Department of Pathology, CHU, Imag'IN Platform, IUCT-Oncopole, Toulouse, France., Sales de Gauzy J; Department of Orthopedic, Trauma and Plastic Surgery, CHU, Toulouse, France., Valentin T; Department of Medical Oncology, Sarcoma, IUCT-Oncopole, Toulouse, France., Castex MP; Department of Medical Oncology, Department of Pediatric Oncology, CHU Toulouse, France., Vérité C; Department of Medical Oncology, Department of Pediatric Oncology, CHU Bordeaux, France., Lorthois S; Institut de Mécanique des Fluides de Toulouse, UMR 5502 CNRS, INPT, University of Toulouse, Toulouse, France., Quintard M; Institut de Mécanique des Fluides de Toulouse, UMR 5502 CNRS, INPT, University of Toulouse, Toulouse, France., Swider P; Institut de Mécanique des Fluides de Toulouse, UMR 5502 CNRS, INPT, University of Toulouse, Toulouse, France., Faruch M; Department of Osteoarticular Diagnostic and Interventional Imaging, CHU, Purpan, Toulouse, France., Assemat P; Institut de Mécanique des Fluides de Toulouse, UMR 5502 CNRS, INPT, University of Toulouse, Toulouse, France.
Jazyk:	angličtina
Zdroj:	Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2024 Sep; Vol. 104 (9), pp. 102122. Date of Electronic Publication: 2024 Aug 02.
DOI:	10.1016/j.labinv.2024.102122
Abstrakt:	The assessment of chemotherapy response in osteosarcoma (OS) based on the average percentage of viable cells is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and ≥10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P < .01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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