干旱区生态环境知识资源中心(Arid): Canine osteosarcoma checkpoint expression correlates with metastasis and T-cell infiltrate

Arid

DOI	10.1016/j.vetimm.2020.110169
	Canine osteosarcoma checkpoint expression correlates with metastasis and T-cell infiltrate
	Cascio, Matthew J.; Whitley, Elizabeth M.; Sahay, Bikash; Cortes-Hinojosa, Galaxia; Chang, Lung-Ji; Cowart, Jonathan; Salute, Marc; Sayour, Elias; Dark, Michael; Sandoval, Zachary; Mitchell, Duane A.; Milner, Rowan J.
通讯作者	Cascio, MJ (corresponding author), Univ Florida, Coll Med, Dept Pediat, Pediat Hematol Oncol, 1600 SW Archer Rd,RMHD204,POB 100298, Gainesville, FL 32610 USA.
来源期刊	VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
ISSN	0165-2427
EISSN	1873-2534
出版年	2021
卷号	232
英文摘要	Background: Immune-targeted therapies are being successfully implemented into cancer clinical practice. In particular checkpoint inhibitors are employed to modulate the immune microenvironment of solid tumors. We sought to determine the expression of PD-L1, HVEM, and B7H3 in human and canine osteosarcoma, and correlate expression with clinical features and tumor infiltrating lymphocytes in naturally-occurring canine osteosarcoma. Methods: Flow cytometry was used to measure ligand surface expression of five human and three canine cell lines. Immunohistochemistry was utilized for expression of ligands and lymphocyte markers in thirty-seven treatment-naive canine osteosarcoma patients. Results: All cell lines expressed all three ligands at variable levels in both species. Metastatic lesions were associated with higher expression of all three ligands in patient tumor samples. PD-L1 expression strongly correlated with B7H3 and HVEM expression, while HVEM and B7H3 were weakly correlated. Whereas peritumoral T-cell expression positively correlated with PD-L1 and HVEM tumor expression, the presence of T-cells intratumorally were rare. Furthermore, intratumor penetration by T-cells was greatest in metastatic lesions, despite log-fold increases in peritumoral T-cells. In summary, PD-L1, HVEM, and B7H3 are expressed in osteosarcoma, with metastatic disease lesions expressing higher levels. We show for the first time that these ligands expressed on osteosarcoma cells positively correlate with each other and the presence of peritumoral T cell infiltration. Furthermore, osteosarcoma appears to be an intratumoral immune desert with significant resistance to effector T cells. Multiple agents targeting checkpoints are in clinical practice, and may have immune modulating benefit in osteosarcoma.
英文关键词	Cancer Dog Immune process Immunotherapy Osteosarcoma T-lymphocytes
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000611846200006
WOS关键词	PROGNOSTIC-SIGNIFICANCE ; SUPPRESSOR-CELLS ; B7-H3 EXPRESSION ; GASTRIC-CANCER ; TUMOR ; SURVIVAL ; BTLA ; HVEM ; STIMULATION ; LYMPHOCYTES
WOS类目	Immunology ; Veterinary Sciences
WOS研究方向	Immunology ; Veterinary Sciences
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/351934
作者单位	[Cascio, Matthew J.; Sayour, Elias] Univ Florida, Coll Med, Dept Pediat, Pediat Hematol Oncol, 1600 SW Archer Rd,RMHD204,POB 100298, Gainesville, FL 32610 USA; [Whitley, Elizabeth M.] Pathologist Pathogenesis LLC, POB 140164, Gainesville, FL 32614 USA; [Sahay, Bikash] Univ Florida, Coll Vet, Dept Infect Dis & Pathol, Med, POB 100880,2015 SW 16th Ave, Gainesville, FL 32610 USA; [Cowart, Jonathan; Salute, Marc; Milner, Rowan J.] Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, POB 100126,2015 SW 16th Ave, Gainesville, FL 32610 USA; [Chang, Lung-Ji] Univ Florida, Mol Genet & Microbiol, POB 100266, Gainesville, FL 32610 USA; [Sayour, Elias; Mitchell, Duane A.] Univ Florida, Dept Neurosurg, POB 100265, Gainesville, FL 32610 USA; [Dark, Michael] Univ Florida, Dept Comparat Diagnost & Populat Med, POB 100123,2015 SW 16th Ave, Gainesville, FL 32610 USA; [Sandoval, Zachary] Univ Florida, Coll Publ Hlth & Hlth Profess, 2015 SW 16th Ave, Gainesville, FL 32608 USA; [Cortes-Hinojosa, Galaxia] Pontificia Univ Cato...
推荐引用方式 GB/T 7714	Cascio, Matthew J.,Whitley, Elizabeth M.,Sahay, Bikash,et al. Canine osteosarcoma checkpoint expression correlates with metastasis and T-cell infiltrate[J],2021,232.
APA	Cascio, Matthew J..,Whitley, Elizabeth M..,Sahay, Bikash.,Cortes-Hinojosa, Galaxia.,Chang, Lung-Ji.,...&Milner, Rowan J..(2021).Canine osteosarcoma checkpoint expression correlates with metastasis and T-cell infiltrate.VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY,232.
MLA	Cascio, Matthew J.,et al."Canine osteosarcoma checkpoint expression correlates with metastasis and T-cell infiltrate".VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 232(2021).