Exceptional response to PD-1 inhibition immunotherapy in advanced metastatic osteosarcoma with tumor site infection

Recent clinical trials have demonstrated a lack of activity of immune checkpoint inhibitors (ICIs) against osteosarcoma. Previous clinical observations have demonstrated a potential immune-stimulatory effect of tumor site infection for osteosarcoma patients. However, whether such infection could aug...

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Bibliographic Details
Published in:Journal for immunotherapy of cancer 2022-09, Vol.10 (9), p.e004673
Main Authors: Li, Meng, Bao, Qiyuan, Zhang, Zhusheng, Wang, Beichen, Liu, Zhuochao, Wen, Junxiang, Wan, Rong, Shen, Yuhui, Zhang, Weibin
Format: Article
Language:English
Subjects:
Bacterial infections
Biomarkers
Biopsy
Bone cancer
Cancer
Case Report
Case Reports
Clinical trials
Cytokines
Debridement
Gene expression
Hypotheses
Immunoassay
Immunotherapy
Infections
Lymphocytes
Medical prognosis
Metastasis
Patients
Pleural effusion
Sarcoma
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Summary:Recent clinical trials have demonstrated a lack of activity of immune checkpoint inhibitors (ICIs) against osteosarcoma. Previous clinical observations have demonstrated a potential immune-stimulatory effect of tumor site infection for osteosarcoma patients. However, whether such infection could augment the efficacy of immunotherapy such as ICIs is currently unknown. Here we report a case of a heavily pretreated 14-year-old boy with pulmonary metastatic osteosarcoma, who has suffered from multiple wound infections and thoracic empyema after previous metastasectomy. Despite the ongoing tumor site infection, the patient had a rapid and durable (11 months) remission of the metastatic lesions after the administration of the Programmed cell death-1(PD-1) inhibitor camrelizumab. No serious ICI-related toxicities or worsening of the infection were noticed during the treatment. Correlative analysis suggested that intratumoral CD8+ T cell infiltration, Programmed death-ligand 1(PD-L1) expression and IFN-γ expression were increased in the tumor microenvironment postinfection versus preinfection. Furthermore, using RNA-seq gene expression analysis, we found a variety of checkpoint targets were also upregulated such as CD200, TIGIT, LAG3, etc. Our report supports the hypothesis of tumor site infection as a potential synergistic mechanism in the tumor microenvironment for ICI immunotherapy.
ISSN:2051-1426
2051-1426
DOI:10.1136/jitc-2022-004673