RT Journal Article
SR Electronic
T1 The efficacies and biomarker investigations of anti-programmed death-1 (anti-PD-1)-based therapies for metastatic bone and soft tissue sarcoma
JF Cancer Biology & Medicine
JO Cancer Biology & Medicine
FD China Anti-Cancer Association
SP 910
OP 930
DO 10.20892/j.issn.2095-3941.2021.0270
VO 19
IS 6
A1 Jia Lu
A1 Ting Li
A1 Zhichao Liao
A1 Hui Yu
A1 Yongtian Zhao
A1 Haixiao Wu
A1 Zhiwu Ren
A1 Jun Zhao
A1 Ruwei Xing
A1 Sheng Teng
A1 Yun Yang
A1 Xiangchun Li
A1 Kexin Chen
A1 Jonathan Trent
A1 Jilong Yang
YR 2022
UL http://www.cancerbiomed.org/content/19/6/910.abstract
AB Objective: Sarcomas are a group of rare malignancies with various subtypes. Patients with metastatic sarcoma who have failed traditional treatments can possibly achieve better prognoses from using novel therapies, including anti-programmed death-1 (PD-1)-based therapies.Methods: We retrospectively analyzed clinical data of 24 metastatic sarcoma patients from June 15, 2016 to December 30, 2019. These patients mainly received angiogenesis inhibitors combined with anti-PD-1 therapy after they became resistant to traditional treatments. Furthermore, 8 patients underwent panel DNA and whole transcript sequencing.Results: Six patients received 2 cycles of anti-PD-1 therapy and were included in the safety evaluation only group. The median follow-up time was 5.77 months. The median progression-free survival was 7.59 months, the overall response rate was 16.7% and the disease control rate was 55.6%. Based on whole exome and transcript sequencing data, there was no association between TMB, TNB, MSI, HLA-LOH, and PD-L1 expressions and sarcoma types with clinical responses. Immunotherapy efficacy and bioinformatics analyses indicated higher intratumoral heterogeneity (ITH) in progressive disease (PD) patients and lower ITH in partial response (PR) and stable disease patients. A higher percentage of immune cell infiltration, especially monocytes, was observed in PR patients. Active stromal gene expression was increased in PD patients but decreased in PR patients. Enrichment analysis revealed that an increased TGF-β signaling pathway was reversely correlated with anti-PD-1 efficacy, while a decreased inflammatory response signaling pathway was positively correlated with anti-PD-1 efficacy.Conclusions: Our study showed PD-1 inhibitors combined with anti-angiogenesis agents were effective and well-tolerated. ITH, monocyte ratio, stroma subtypes, and the status of immune-associated signaling pathways may be related with anti-PD-1 based therapy.