Journal: Cancer Immunology Research

Article Title: CD161 Characterizes an Inflamed Subset of Cytotoxic T Lymphocytes Associated with Prolonged Survival in Human Papillomavirus–Driven Oropharyngeal Cancer

doi: 10.1158/2326-6066.CIR-22-0454

Figure Lengend Snippet: The phenotype and function of CD161 + CTLs. A, Heat map displaying expression values of discriminative genes between KLRB1 − and KLRB1 + CTLs (from clusters 0, 2, 3, and 9) based on the data from single-cell RNA sequencing. B, Scores for the terminal exhaustion signature, tissue-resident memory T-cell signature, and chemokine/IFNγ signature in KLRB1 − and KLRB1 + CTLs based on the data from single-cell RNA sequencing. C, Coexpression of cytotoxic cytokines and inhibitory receptors on CD161 − or CD161 + CTLs in OPSCC biopsies ( n = 13–19) via flow cytometry, paired Student t test. D, MFI of cytotoxic cytokines coexpressed on CD161 − or CD161 + CTLs treated with PD-1 or CD39 blocking antibodies in OPSCC biopsies ( n = 7–8), paired Student t test. E, MFI of IFNγ coexpressed on CD161 + CTLs treated with CD161-blocking antibodies for 72 hours in HPV + biopsies ( n = 3) and blood samples ( n = 4), paired Student t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001. n.s.: no statistical significance.

Article Snippet: For the checkpoint blockade experiment, cryopreservated TILs or PBMCs were thawed, expanded, and seeded (5 × 10 5 cells/well) as described, and treated with PD-1 blocking monoclonal antibody (mAb; BioLegend, clone EH12.2H7, cat. #329926, 10 μg/mL), CD39 blocking mAb (Bio-Rad, clone A1, cat. #MCA1268EL, 10 μg/mL), or Tim-3 blocking mAb (BioLegend, clone F28-2E2, cat. #345004, 10 μg/mL) for 7 days.

Techniques: Expressing, RNA Sequencing, Flow Cytometry, Blocking Assay

Journal: Heliyon

Article Title: Pharmacodynamics of Sishen decoction in relieving rheumatoid arthritis: Chemical composition, regulatory pathway and online prediction simulation

doi: 10.1016/j.heliyon.2024.e37257

Figure Lengend Snippet: SSD treatment ameliorated RA rats. Representative images of hind paws from different groups and changes in foot circumference. Hematoxylin eosin staining and immunohistochemical staining (CD31, CD39, CD73, CCR6 and IL1R1) of knee joint synovial slices. * P < 0.05, ** P < 0.01 vs Model group.

Article Snippet: Additionally, antibodies for IL1R1, CD39, CD73, and CCR6 were obtained from Bosterbio in Wuhan, China.

Techniques: Staining, Immunohistochemical staining

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: The two ectonucleotidases CD39 and CD73 control the metabolic fate of ATP and adenosine in the extracellular environment. Extracellular ATP is converted into its metabolites ADP and AMP sequentially by CD39, which is then further metabolized to adenosine by CD73. Activated CD39/CD73/A2AR signaling within the TME will suppress the function of antitumor immune cells (T cells, B cells, NK cells, and DCs) but promote the activity of the regulatory immune cells (MDSCs and Tregs), thus giving rise to a immunosuppressive TME. Notes: TME: tumor microenvironment; NK: natural killer; DCs: dendritic cells; MDSC: myeloid-derived suppressor cells; Treg: regulatory T cells; Th17: T helper 17 cells

Article Snippet: Combination TTX-030 with immunotherapy and/or chemotherapy , Trishula Therapeutics, Inc. AbbVie , Anti-CD39 antibody with immunotherapy , Phase I , NCT04306900.

Techniques: Control, Activity Assay, Derivative Assay

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Gene-expression landscape of the three major components (CD39, CD73 and A2AR) in the adenosine signaling pathway in various solid cancer types. The Cancer Genome Altas (TCGA) analysis RNA-sequencing (RNA-seq) data of ENTPD1( A ), NT5E ( B ) and ADORA2A ( C ), encoding the proteins CD39, CD73, A2AR, respectively, in human cancers. Notes: LUAD: lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; PRAD: Prostate; HNSC: Head and Neck squamous cell; KIRC: Kidney renal clear cell carcinoma; UCEC: Uterinecorps Endometrial carcinoma; PCPG: Pheochromocytoma; LIHC: Liver hepatocellular carcinoma; COAD: Colon adenocarcinoma; READ: Rectum adenocarcinoma; PAAD: Pancreatic adenocarcinoma; BLCA: Bladder Urothelial Carcinoma; CESC: Cervical squamous cell carcinoma; CHOL: Cholangiocarcinoma; ESCA: Esophageal carcinoma; KICH: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; STAD: Stomach adenocarcinoma; THYM: Thyroid carcinoma; THCA: Thyroid carcinoma; BRCA: Breast invasive carcinoma; GBM: Glioblastoma multiforme. N = normal tissue; T = tumor specimen

Article Snippet: Combination TTX-030 with immunotherapy and/or chemotherapy , Trishula Therapeutics, Inc. AbbVie , Anti-CD39 antibody with immunotherapy , Phase I , NCT04306900.

Techniques: Gene Expression, RNA Sequencing

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Investigation of monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway in clinical trials. ( https://clinicaltrials.gov/ )

Article Snippet: Combination TTX-030 with immunotherapy and/or chemotherapy , Trishula Therapeutics, Inc. AbbVie , Anti-CD39 antibody with immunotherapy , Phase I , NCT04306900.

Techniques: Bioprocessing, Clinical Proteomics

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Combinations of CD39/CD73/A2AR inhibitors and other cancer therapies under investigation in clinical trials ( https://clinicaltrials.gov/ )

Article Snippet: Combination TTX-030 with immunotherapy and/or chemotherapy , Trishula Therapeutics, Inc. AbbVie , Anti-CD39 antibody with immunotherapy , Phase I , NCT04306900.

Techniques: Clinical Proteomics

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Biomarkers related to the CD39/CD73/A2AR pathway in cancer

Article Snippet: Combination TTX-030 with immunotherapy and/or chemotherapy , Trishula Therapeutics, Inc. AbbVie , Anti-CD39 antibody with immunotherapy , Phase I , NCT04306900.

Techniques: Gene Expression, Expressing, Activity Assay, Diagnostic Assay, Biomarker Discovery, Blocking Assay

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: The two ectonucleotidases CD39 and CD73 control the metabolic fate of ATP and adenosine in the extracellular environment. Extracellular ATP is converted into its metabolites ADP and AMP sequentially by CD39, which is then further metabolized to adenosine by CD73. Activated CD39/CD73/A2AR signaling within the TME will suppress the function of antitumor immune cells (T cells, B cells, NK cells, and DCs) but promote the activity of the regulatory immune cells (MDSCs and Tregs), thus giving rise to a immunosuppressive TME. Notes: TME: tumor microenvironment; NK: natural killer; DCs: dendritic cells; MDSC: myeloid-derived suppressor cells; Treg: regulatory T cells; Th17: T helper 17 cells

Article Snippet: SRF617 , Surface Oncology , CD39 antagonist , Phase I , NCT04336098.

Techniques: Control, Activity Assay, Derivative Assay

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Gene-expression landscape of the three major components (CD39, CD73 and A2AR) in the adenosine signaling pathway in various solid cancer types. The Cancer Genome Altas (TCGA) analysis RNA-sequencing (RNA-seq) data of ENTPD1( A ), NT5E ( B ) and ADORA2A ( C ), encoding the proteins CD39, CD73, A2AR, respectively, in human cancers. Notes: LUAD: lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; PRAD: Prostate; HNSC: Head and Neck squamous cell; KIRC: Kidney renal clear cell carcinoma; UCEC: Uterinecorps Endometrial carcinoma; PCPG: Pheochromocytoma; LIHC: Liver hepatocellular carcinoma; COAD: Colon adenocarcinoma; READ: Rectum adenocarcinoma; PAAD: Pancreatic adenocarcinoma; BLCA: Bladder Urothelial Carcinoma; CESC: Cervical squamous cell carcinoma; CHOL: Cholangiocarcinoma; ESCA: Esophageal carcinoma; KICH: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; STAD: Stomach adenocarcinoma; THYM: Thyroid carcinoma; THCA: Thyroid carcinoma; BRCA: Breast invasive carcinoma; GBM: Glioblastoma multiforme. N = normal tissue; T = tumor specimen

Article Snippet: SRF617 , Surface Oncology , CD39 antagonist , Phase I , NCT04336098.

Techniques: Gene Expression, RNA Sequencing

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Investigation of monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway in clinical trials. ( https://clinicaltrials.gov/ )

Article Snippet: SRF617 , Surface Oncology , CD39 antagonist , Phase I , NCT04336098.

Techniques: Bioprocessing, Clinical Proteomics

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Combinations of CD39/CD73/A2AR inhibitors and other cancer therapies under investigation in clinical trials ( https://clinicaltrials.gov/ )

Article Snippet: SRF617 , Surface Oncology , CD39 antagonist , Phase I , NCT04336098.

Techniques: Clinical Proteomics

Journal: Molecular Cancer

Article Title: CD39/CD73/A2AR pathway and cancer immunotherapy

doi: 10.1186/s12943-023-01733-x

Figure Lengend Snippet: Biomarkers related to the CD39/CD73/A2AR pathway in cancer

Article Snippet: SRF617 , Surface Oncology , CD39 antagonist , Phase I , NCT04336098.

Techniques: Gene Expression, Expressing, Activity Assay, Diagnostic Assay, Biomarker Discovery, Blocking Assay

Journal: International Journal of Molecular Sciences

Article Title: CD39 Regulation and Functions in T Cells

doi: 10.3390/ijms22158068

Figure Lengend Snippet: Effects of targeting CD39 on T cells. ( A ) CD39 or CD73 blocking by pharmacological compounds (i.e., POM1 and ARL7156 or small-molecule inhibitors) or by using antibodies in in vivo systems decreases the suppressive activities of FOXP3 + Treg cells. ( B ) Targeting CD39 or CD73 in CD8 T cells effects an increase in effector and cytotoxic T cell functions, mediated by IFN-γ and TNF-α production and CD107a upregulation. ( C ) Targeting CD39 or CD73 in CD4 T cells increases Th1 cytokine (IFN-γ, TNF-α and IL-2) and IL-21 production, which (was recently found to be) is responsible for B cell differentiation.

Article Snippet: Similarly, a CD39 blocking antibody (IPH520) was recently developed by Innate Pharma and entered in a recent clinical trial (NCT04261075) with the objective of studying IPH5201 as a monotherapy or in combination with anti-PDL1 (Durvalumab) and/or anti-CD73 (Oleclumab).

Techniques: Blocking Assay, In Vivo, Cell Differentiation