Single-cell dissection of persistent tumor antigens in non-responders reveals opportunities for TAA-targeted vaccination after neoadjuvant therapy in esophageal squamous cell carcinoma

Background
Neoadjuvant immune checkpoint blockade (ICB) combined with chemotherapy has demonstrated higher response rates than chemotherapy alone in resectable esophageal squamous cell carcinoma (ESCC). Although tumor microenvironment (TME) features a…

Single-cell and spatial transcriptomics reveal that the CXCL12-CXCR4 axis drives the immune-desert phenotype in small cell lung cancer by recruiting immunosuppressive CXCR4+ neutrophils and S100A8+ monocytes

Background
Small cell lung cancer (SCLC) is a recalcitrant malignancy with limited responses to immunotherapy, largely due to its uniquely immunosuppressive tumor microenvironment (TME). However, the molecular mechanisms driving this phenotype remain …

Precision modeling of tumor antigen-specific T-cell responses in humanized mice for preclinical assessment of cancer immunotherapies

Background
Humanized mice are highly valuable models for the preclinical development of cancer immunotherapies. However, conventional models often fail to mount robust and trackable tumor antigen-specific (TA-specific) T-cell responses, which hinders …

Non-enzymatic Rnaseh2c orchestrates proliferating macrophage-driven immunosuppression and HCC progression via Cdk9 proliferation axis and CCL2/CCR2-mediated CD8+ Tex infiltration: a novel therapeutic paradigm with “Rnaseh2c-In1” inhibitor

Background
Tumor-associated macrophages are pivotal drivers of hepatocellular carcinoma (HCC) progression. However, the functional contributions of proliferating macrophages (Prolif Ms) within the tumor microenvironment (TME) remain poorly defined.

M…

Stem-like PD-1+TCF-1+ CD8+ T cells result from helpless priming and rely on CD4+ T-cell help to complete their cytotoxic effector differentiation

Background
Antigen-specific CD8+ T cells can be in a stem-like programmed cell death protein-1 (PD-1)+TCF-1+ differentiation state that progresses into terminal exhaustion in cancer and chronic infection. These stem-like cells are important, since the…

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 …

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