Expression of B7-H3 in cancer tissue during osteosarcoma progression in nude mice

Abstract

ABSTRACT. Immune cells might participate in the ontogenesis of osteosarcoma. B7-H3 is a new discovered T cell co-stimulatory molecule that was found to be overexpressed in malignant tumors. We aimed to investigate the dynamic expression level of B7-H3 in nude mice with osteosarcoma. A nude mouse osteosarcoma model was successfully established. B7-H3 expression and distribution changes in the early, middle, and late phases of osteosarcoma formation after tumor implantation were observed. Reverse transcription-polymerase chain reaction and western blot analyses were applied to measure the B7-H3 mRNA and protein dynamic changes. Confocal microscopy and immunohistochemistry were used to determine B7-H3 localization and CD3+ T cell expression, respectively, in osteosarcoma tissue. B7-H3 mRNA and protein levels fluctuated during the process of osteosarcoma formation in the nude mouse model. Expression levels were lower in the early and middle phases, while B7-H3 mRNA and protein were overexpressed in the late stage. Accordingly, CD3+ T cell numbers in the early, middle, and late phases in osteosarcoma tissue were 93 ± 13, 92 ± 12, and 46 ± 15, respectively; they can be seen to have decreased significantly in the late stage (P < 0.05). Overall, our results indicated that the B7-H3 expression level is correlated with tumor volume and severity; therefore, it might serve as a tumor biomarker for osteosarcoma.

New checkpoints in cancer immunotherapy

“…Recent studies found aberrant B7‐H3 expression on a wide variety of cancers, including stomach, lung, prostate, kidney, ovary, endometrium, colorectum, pancreas, liver, oral, bladder and breast …”

Roles of B7-H3 in Cervical Cancer and Its Prognostic Value

“…It plays key roles in initial antigen priming by binding with an as yet undiscovered receptor, and its expression can be induced on dendritic cells or monocytes by inflammatory cytokines 3 . It has been reported that B7-H3 is expressed in numerous human malignancies, such as osteosarcoma, breast cancer, renal cell carcinoma, lung cancer, oesophageal cancer, prostate cancer, oral cancer, pancreatic cancer, and colorectal cancer 4 - 11 . All these reports suggested that the aberrant expression of B7-H3 might lead to carcinogenesis through various of mechanisms and is an indicator of poor prognosis in cancer patients.…”

Bone sarcomas in the immunotherapy era

“…Numerous recent publications have demonstrated the expression of immune checkpoints by bone sarcomas in order to escape immune surveillance. For example, osteosarcoma and chondrosarcoma express PDL-1/PDL-2 [Thanindratarn et al, 2019;McEachron et al, 2018;Yang et al, 2018;Sandara et al, 2017;van Erp et al, 2017], B7-H3 [Yin et al, 2015;Wang et al, 2013], HHLA-2 [Koirala et al, 2016]. B7-H4 is expressed by osteosarcoma cells [Dong et al, 2015].…”

“…Numerous recent publications have demonstrated the expression of immune checkpoints by bone sarcomas in order to escape immune surveillance. For example, osteosarcoma and chondrosarcoma express PDL1/PDL2 (McEachron, Triche, Sorenson, Parham, & Carpten, 2018; Sundara et al, 2017; Thanindratarn, Dean, Nelson, Hornicek, & Duan, 2019; van Erp et al, 2017; Yang et al, 2018; Zheng et al, 2018), B7‐H3 (Wang et al, 2013; Yin, Wang, & Zhang, 2015) and HHLA‐2 (Koirala et al, 2016). B7‐H4 is expressed by osteosarcoma cells (Dong & Ma, 2015).…”