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Immuno-oncology

Studies that investigate the immune system, its interactions with tumor cells, and opportunities to enhance the body's natural defenses against cancer

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Latest in Immuno-oncology
September 26 2024
DNA Methylation-Derived Immune Cell Proportions and Cancer Risk in Black Participants
Christopher S. Semancik, Naisi Zhao et al.
Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers ...
September 25 2024
A precision engineered interleukin-2 (IL-2) for bolstering CD8+ T- and NK-cell activity without eosinophilia and vascular leak syndrome in non-human primates
Lina Ma, Nicole V Acuff et al.
We have created a precisely pegylated IL-2 [SAR-444245 (SAR’245) or pegenzileukin, previously THOR- 707] designed for proliferation of target CD8+ T and NK cells for anti-cancer activity, with minimal expansion of anti-target regulatory CD4+ T cells (Tregs) that counter their action, or eosinophils that trigger vascular ...
September 25 2024
Peripheral blood interferon responses to toll-like receptor 1/2 signaling associate with longer survival in men with metastatic prostate cancer treated with Sipleucel-T.
Michael C Brown, Vincent M D'Anniballe et al.
Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival after sipuleucel-T (sip-T) therapy, an FDA-approved, autologous cell therapy. We ...
September 18 2024
Peroxisome proliferator-activated receptor δ suppresses the cytotoxicity of CD8+ T cells by inhibiting RelA DNA binding activity
Bo Cen, Jie Wei et al.
The molecular mechanisms regulating CD8+ cytotoxic T lymphocytes (CTLs) are not fully understood. Here, we show that the peroxisome proliferator-activated receptor ƍ (PPAR-δ) suppresses CTL cytotoxicity by inhibiting RelA DNA binding. Treatment of ApcMin/+ mice with the PPAR-δ agonist GW501516 reduced the activation of ...
June 28 2024
First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study
Duncan A. Wheatley, Rossana Berardi et al.
Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non–small cell lung cancer (NSCLC).
June 26 2024
Transcriptome Deconvolution Reveals Absence of Cancer Cell Expression Signature in Immune Checkpoint Blockade Response
Yu Amanda Guo, Tanmay Kulshrestha et al.
Immune checkpoint therapy (ICB) has conferred significant and durable clinical benefit to some patients with cancer. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors ...
June 21 2024
Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response
Robert J. Norgard, Pratha Budhani et al.
KRAS inhibitors have demonstrated exciting preclinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KrasG12D, p53-mutant, murine pancreatic ductal adenocarcinoma–derived cell lines (KPCY) to ...
June 18 2024
HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity
Priyanka S. Rana, James J. Ignatz-Hoover et al.
Proteasomes degrade intracellular proteins to generate antigenic peptides that are recognized by the adaptive immune system and promote anticancer immunity. However, tumors subvert the antigen presentation machinery to escape immunosurveillance. We hypothesized that proteasome activation could concomitantly increase ...
June 10 2024
Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis
Armin Rashidi, Maryam Ebadi et al.
Acute GVHD (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation ...
June 04 2024
B7-H3–Targeting Chimeric Antigen Receptors Epstein-Barr Virus–specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3–positive Solid Tumors
Siok Ping Yeo, Lindsay Kua et al.
Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3–targeting domain in our CAR construct to circumvent the ...
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