PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity

Background Anti-programmed cell death protein 1 (anti-PD-1) antibodies have achieved revolutionary success in cancer therapy. However, the impact of anti-PD-1 therapy on host humoral immunity in humans during cancer immunotherapy requires further investigation. Methods We evaluated immunoglobulin titers by ELISA and screened the immune landscape of immune cells from 25 healthy donors and 50 cases… Continue reading PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity

Scientists engineer CRISPR enzymes that evade the immune system

The core components of CRISPR-based genome-editing therapies are bacterial proteins called nucleases that can stimulate unwanted immune responses in people, increasing the chances of side effects and making these therapies potentially less effective. Researchers at the Broad Institute of MIT and Harvard and Cyrus Biotechnology have now engineered two CRISPR nucleases, Cas9 and Cas12, to… Continue reading Scientists engineer CRISPR enzymes that evade the immune system

Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway

Background Immunosuppressive phenotype compromised immunotherapy efficacy of hepatocellular carcinoma. Tumor cells intrinsic mitochondria dynamics could pass effects on the extracellular microenvironment through mtDNA stress. PGAM5 anchors at mitochondria and regulates mitochondria functions. We aim to explore whether the regulation of tumor-intrinsic PGAM5 on mitochondria affects tumor-infiltrating immune cells in the microenvironment and whether tumor-intrinsic PGAM5… Continue reading Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway

Nivolumab plasma concentration and clearance associated with overall survival in patients with renal cell carcinoma

Background Nivolumab is an immune checkpoint inhibitor (ICI) that selectively inhibits programmed cell death protein 1 activation, restoring antitumor immunity. ICIs are indicated for various types of advanced solid tumors; however, not all patients benefit from them, and tools that could be used in the clinic to predict response to treatment represent an unmet need.… Continue reading Nivolumab plasma concentration and clearance associated with overall survival in patients with renal cell carcinoma

Novel and potent MICA/B antibody is therapeutically effective in KRAS LKB1 mutant lung cancer models

Background Concurrent KRAS LKB1 (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells. Methods Expression of NK cell activating ligands in… Continue reading Novel and potent MICA/B antibody is therapeutically effective in KRAS LKB1 mutant lung cancer models

Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export

ABCC1 mediates the export of cGAMP, but the underlying molecular mechanism of cGAMP recognition and export is not clear. Here, Shinde et al. show that human ABCC1 forms a dimer in vitro and in vivo. Cryo-EM structures of ligand-free and cGAMP-bound ABCC1 reveal the molecular basis of cGAMP recognition and export.

Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma

Background Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its potential antitumor effects in several preclinical renal cancer models. Methods Ad vaccines… Continue reading Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma

Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors

Background Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy. Therefore, investigating how TME components in MM influence ICB treatment is urgent. Methods We employed two well-established… Continue reading Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors