Sensory neuron-derived CCL5 orchestrates an immunosuppressive niche via regulatory T cells to fuel head and neck tumor progression

Background
Perineural invasion (PNI) is a hallmark of malignancy in solid tumors, including oral squamous cell carcinoma (OSCC), and is closely associated with poor prognosis. Emerging evidence suggests a critical association between PNI and the tumor…

VISTA neutralization by immunization reprograms immunosuppression and augments vaccine efficacy in renal carcinoma

Background
Renal carcinoma remains a highly lethal malignancy, and tumor vaccine efficacy is frequently hampered by a profoundly immunosuppressive tumor microenvironment. V-domain Ig suppressor of T-cell activation (VISTA), an inhibitory immune checkp…

Phase 1 multicenter study of the NKG2A targeting antibody S095029 as a single agent and in combination with anti-PD-1 in patients with advanced malignancies

Background
NKG2A is a C-type lectin that heterodimerizes with CD94 creating an inhibitory immunoreceptor. S095029 is a fully human monoclonal IgG1 anti-NKG2A antibody with attenuated Fc-effector functions that specifically binds the NKG2A/CD94 heterod…

LGALS9 blockade augments vaccine-induced immune responses against prostate cancer

Background
Prostate-specific membrane antigen (PSMA)-based vaccination represents a promising immunotherapeutic strategy for prostate cancer; however, its efficacy remains constrained by tumor-induced immune evasion and insufficient activation of anti…

PSCA CAR V{delta}1 T cells: a safer off-the-shelf CAR T therapy for pancreatic cancer?

Pancreatic cancer remains among the deadliest malignancies, with a 5-year survival of ~13%. Chimeric antigen receptor (CAR) T -cell therapy offers hope, but conventional αβ T cells can trigger severe toxicities, including graft-versus-host …

Endogenous neoantigen-specific antibodies mediate antitumor responses and determine vaccine efficacy

Background
The contribution of B cells to antitumor immunity remains controversial, with studies reporting varied effects across cancer types. Even less is known about the role of the endogenous humoral response, including when tumor-elicited antibodi…

Correlation between recognition of autologous tumor organoids by tumor-infiltrating lymphocytes from metastatic epithelial cancers and clinical response

Background
Neoantigen-specific tumor-infiltrating lymphocytes (TILs) have the ability to mediate responses in patients with metastatic epithelial cancers. While some identified factors are associated with response, there is a need for ways to determin…

Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma

Purpose
Aberrant alternative splicing (AS) events have been implicated in cancer progression; however, their role in metastatic renal cell carcinoma (mRCC) remains underexplored. This study aims to identify AS events associated with clinical benefits …

CAR-engineering of innate and innate-like immune cells: a new horizon in adoptive cell therapy for solid tumors

Background
Chimeric antigen receptor (CAR) therapies have revolutionized cancer immunotherapy, particularly in hematologic malignancies, but their efficacy in solid tumors remains limited. Key barriers include tumor antigen heterogeneity, on-target/of…

Discontinuation of combo immunotherapy and outcome of patients with melanoma brain metastases

Background
Nivolumab plus ipilimumab (COMBO) is the standard treatment for asymptomatic melanoma brain metastases (MBM), but current guidelines do not provide specific recommendations for treatment discontinuation in responding patients. This study ai…

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