Effectiveness evaluation of dendritic cell immunotherapy for osteosarcoma on survival rate and in vitro immune response

Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.

Section: Discussionmentioning

confidence: 99%

Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma

Koirala

Roth

Gill

et al. 2016

Sci Rep

222

219

“…Numerous immunotherapies were assessed to modulate the tumor microenvironment and to reactivate a prolonged and efficient immune response [6]. Adoptive cell therapies based on TIL as described above and generating antigen-specific lymphocytes [103][104][105], dendritic cells [106][107][108][109][110][111][112], NK cells [113][114][115][116][117][118] were developed mostly in vitro and in pre-clinical model of osteosarcoma. Several clinical trials are currently in progress for evaluating their therapeutic efficacy in patients (Table 1).…”

Section: Lymphocytes Subpopulations In Osteosarcoma and Therapeutic Imentioning

confidence: 99%

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

Lezot

2019

Cellular Immunology

171

183

“…Effective anti-cancer therapies alone or in combination have thus been designed in bone sarcomas to stimulate tumor-associated dendritic cell function as a means of driving the antitumor immune response and preclinical results showed promising results [Li et al, 2019;He et al, 2016;Fang et al, 2015;Kawano et al, 2015]. Clinical investigations did not confirm the results of pre-clinical studies.…”

Section: Dendritic Cells For Improving the Immune Recognition Of Bonementioning

confidence: 99%

“…Bone sarcomas expressed specific antigens (Table 1), which have stimulated the development of targeted therapies. Effective anti‐cancer therapies alone or in combination have thus been designed in bone sarcomas to stimulate tumour‐associated dendritic cell function as a means of driving the anti‐tumour immune response and preclinical results showed promising results (Fang, Jiang, & Xia, 2015 ; He, Zhang, Kou, & Tang, 2016 ; Kawano et al, 2015 ; Li, Wang, & Fang, 2019). However, clinical investigations did not confirm the results of preclinical studies.…”

Section: Dendritic Cells For Improving the Immune Recognition Of Bone Sarcoma Cellsmentioning

confidence: 99%

Bone sarcomas in the immunotherapy era

Schiavone

2020

British J Pharmacology

Bone sarcomas are primary bone tumors which occur mainly in children and adolescents, in the form of osteosarcoma and Ewing sarcoma, and in people in their 40s, in the form of chondrosarcoma. The last four decades have been characterized by the development of therapeutic approaches based on drug combinations, but with no real improvement in overall survival. Recent progress made in the field of oncoimmunology has made it possible to better understand the crucial role played by immune infiltrate in the oncologic process and has led to recent clinical trials with a common aim: reprogramming the immune system in order to facilitate cancer cell recognition. Similarly, immune infiltrates of bone sarcomas have been characterized and the first molecular profiling identified potential immune therapeutic targets, which have been used for designing ongoing clinical trials. Unfortunately, the objective clinical responses in clinical trials remain anecdotal but highlight the necessity to better characterize tumor microenvironment of bone sarcoma to unlock the immunotherapeutic response especially in their pediatric forms. Bone sarcomas have thus entered the immunotherapy era. The present review gives a brief overview of the most recent developments in immunotherapies in bone sarcomas.