IFN-{gamma} PET imaging stratifies and predicts response to CD137 agonism in a syngeneic colorectal tumor model

Background
The secretion of interferon- (IFN-) by activated immune cells is one of the hallmarks of response to cancer immunotherapy. Hence, detection of this cytokine via imaging can help determine an activated antitumor immune response. We have prev…

Systemic pre-conditioning favors effector over exhausted CD8 T-cell subsets following Sup2-IL33 armored CAR T-cell therapy

Background
Systemic pre-conditioning prior to chimeric antigen receptor (CAR) T-cell infusion enhances engraftment and increases infiltration and activity of adoptively transferred cells within the tumor. Despite promising responses in some patients, …

Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis

Background
Immune checkpoint inhibitor-associated myocarditis (ICIAM) poses significant challenges for cancer immunotherapy, particularly regarding the safety and efficacy of immune checkpoint blockade (ICB) rechallenge.

Methods
The present study ana…

Pretreatment intratumoral mature TLSs in non-clear cell renal cell carcinoma are associated with response to immunotherapy rechallenge

Background
While immune checkpoint inhibitor (ICI)-based therapy has shown promising efficacy in patients with metastatic non-clear cell renal cell carcinoma (nccRCC) in the first-line setting, the optimal treatment following disease progression remai…

CXCR3 signaling promotes Delta One T cell recruitment and antitumor efficacy in colorectal cancer

Immunotherapy has transformed cancer treatment, yet its efficacy in solid tumors, and particularly in colorectal cancer (CRC), remains limited by insufficient infiltration of endogenous or adoptively transferred immune cells. Our group developed Delta…

Complete response to immune checkpoint blockade in sarcomatoid renal cell carcinoma with bone marrow metastasis: case report with tumor immune microenvironment profiling

Bone marrow represents a unique microenvironment enriched with both immunosuppressive cells and immune-activating functions. However, its role in metastasis and response to immunotherapy remains poorly understood. We report a case of sarcomatoid clear…

CLEC2B-KLRB1 axis acts as an immune checkpoint, governing the exhaustion of CD8+ T cells and their resistance to immune checkpoint blockade

Background
Many patients with cancer benefit little from immune checkpoint blockade (ICB), a major obstacle to immunotherapy for decades. Finding alternative immune checkpoints that control CD8+ T-cell exhaustion is urgent if we are to improve the eff…

ATF4 promotes immune evasion in oral squamous cell carcinoma by suppressing autophagic PD-L1 degradation

Background
Immune checkpoint blockade targeting programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) has revolutionized cancer therapy. However, its efficacy is frequently limited by primary and acquired resistance. While inflammatory signals tra…

Comparing immune-checkpoint inhibitor-mediated inflammatory arthritis to polymyalgia rheumatica: a prospective cohort study

Background
Immune checkpoint inhibitor (ICI)-related inflammatory arthritis occurs in approximately 6% of ICI-treated patients, and is often long-lasting. The clinical presentation is heterogeneous, and often loosely resembles either rheumatoid arthri…

FAP-CD40 and PD1-IL2v combination therapy reprograms immunologically cold tumors through de novo intratumoral T cell-dendritic cell clusters

Background
Pancreatic ductal adenocarcinoma (PDAC) remains a major challenge for immunotherapy due to its immunologically cold tumor nature, characterized by poor T cell infiltration and a highly suppressive tumor microenvironment. Here, we propose a …

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