systems that incorporate features of the tumor microenvironment and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocompetent mouse tumor models. MDOTS profiling demonstrated that TBK1/IKKε inhibition enhanced response to PD-1 blockade, which effectively predicted tumor response Systematic profiling of secreted cytokines in PDOTS captured key features associated with response and resistance to PD-1 blockade. Thus, MDOTS/PDOTS profiling represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens. Resistance to PD-1 blockade remains a challenge for many patients, and biomarkers to guide treatment are lacking. Here, we demonstrate feasibility of profiling of PD-1 blockade to interrogate the tumor immune microenvironment, develop therapeutic combinations, and facilitate precision immuno-oncology efforts. .
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http://dx.doi.org/10.1158/2159-8290.CD-17-0833 | DOI Listing |
J Infect Chemother
December 2024
Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan.
Immune checkpoint inhibitors (ICIs) have been approved for treating various cancers; however, they can cause immune-related adverse events. Generally, ICIs are not associated with an increased risk of infection, however, several reports demonstrated infections caused by nontuberculous mycobacterium (NTM) during ICI therapy. Here, we report a case of NTM shoulder arthritis with acute exacerbation immediately after ICI initiation.
View Article and Find Full Text PDFJ Natl Compr Canc Netw
December 2024
1Department of Urology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).
Patients And Methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.
Sci Immunol
December 2024
Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA.
The increasing use of anti-programmed cell death 1 (PD-1) immune checkpoint blockade has led to the emergence of immune-related adverse events (irAEs), including dysfunction of the submandibular gland (SMG). In this study, we investigated the immunoregulatory mechanism contributing to the susceptibility of the SMG to irAEs. We found that the SMGs of PD-1-deficient mice and anti-programmed cell death ligand 1 (PD-L1)-treated mice harbor an expanded population of CD8 T cells.
View Article and Find Full Text PDFInt J Surg
December 2024
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background: RPN1, also known as ribophorin I (RPN1), is a type I transmembrane protein that plays an important role in glycosylation. However, the effects of RPN1 on cancer progression and immune evasion in breast cancer (BC) have not been identified.
Materials And Methods: The expression of RPN1 was evaluated using RT-qPCR and immunohistochemistry (IHC).
Immunotargets Ther
December 2024
Department of Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China.
Introduction: The NLRP3 inflammasome has been implicated in the initiation of inflammation and tumorigenesis; however, its role in epithelial ovarian cancer (EOC) remains unclear.
Methods: This study employed high-throughput sequencing data, ELISA, clone formation assay, Western blot, and flow cytometric analysis to investigate the specific role of the NLRP3 inflammasome in EOC.
Results: NLRP3 was highly expressed in human EOC tissues and correlated with an unfavorable prognosis.
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