CD55-expressing myeloid-derived suppressor cells (MDSCs) drive cancer immunoevasion

Background
Myeloid-derived suppressor cells (MDSCs) play a pivotal role in shaping the immunosuppressive tumor microenvironment, thereby driving tumor progression and contributing to resistance to therapy. The surface molecules expressed on MDSCs serv…

SMAD7 drives natural killer cell antitumor activity through canonical TGF-{beta} blockade and non-canonical transcriptional activation of STAT5A

Background
Natural killer (NK) cells are key effectors in antitumor immunity, yet their function is markedly suppressed by transforming growth factor-β (TGF-β) in the tumor microenvironment. SMAD7 is an established intracellular antagonist o…

Targeting the novel immune checkpoint KLRG1 is markedly therapeutic against cancer through multiple lymphocyte subsets

Background
Checkpoint blockade therapies have demonstrated clinical benefit across multiple cancer types; however, many patients with immune cell infiltration remain non-responsive or develop resistance. This suggests that additional, unidentified reg…

RNA helicase SKIV2L impedes tumor immunity by reprogramming arginine metabolism of hepatocellular carcinomas

Background and aims
Human solid tumors such as hepatocellular carcinomas (HCC) establish a complex immunosuppressive tumor microenvironment (TME) that undermines the efficacy of existing immunotherapies such as chimeric antigen receptor T (CAR T) cell…

TROP2/claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer

Background
Immune exclusion inhibits antitumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. In triple-negative breast cancer (TNBC), an aggressive and generally immune-rich subtype, an immune-cold microenvironment …

Targeting PAR-2 with a negative allosteric modulator increases tumor antigen presentation and potentiates anti-PD-1 immunotherapy

Background
Identifying the mechanisms underlying resistance to immune checkpoint inhibitors (ICIs) has become a major focus in cancer immunotherapy. Our previous work identified F2RL1 expression, encoding the G protein-coupled receptor Protease-Activa…

Transforming growth factor {beta} induced as a novel secreted immune checkpoint counterinhibiting human tumor-associated T cells

Background
We investigated the hypothesis that transforming growth factor β induced (TGFBI), an extracellular matrix protein secreted in the microenvironment of several tumors, can act as a secreted immune checkpoint (sIC) that contributes to the…

Epigenetic remodeling in sarcoma promotes T-cell infiltration via modulation of the Hippo pathway

Background
Insufficient T-cell infiltration limits the effectiveness of immunotherapy in sarcoma, yet the tumor-intrinsic mechanisms that govern immune exclusion remain poorly defined.

Methods
By integrating patient-derived ex vivo sarcoma spheroids …

Influence of USP15 and its derived-peptide on non-small cell lung cancer immune evasion via regulating PD-L1 stability

Background
Immune checkpoint inhibitors (ICIs) therapy targeting programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) shows promising clinical benefits in non-small cell lung cancer (NSCLC). However, the relatively low respons…

HFB301001, an OX40-based immunotherapy, drives Treg clearance and CTL activation through optimized OX40 receptor clustering

Background
OX40, a key co-stimulatory receptor that amplifies T cell-mediated anti-tumor immunity, is a promising immunotherapeutic target. Despite most reported OX40 agonists in clinical trials having high affinity, the relationship between affinity …

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