Pancreatic tumor microenvironment reprogramming via alloantigen-expressing virotherapy elicits tumor rejection and improves immunotherapy response

Background
Pancreatic ductal adenocarcinoma (PDAC), the most common malignant type of pancreatic cancer, is characterized by a dense desmoplastic stroma, low neoantigen burden, and a highly immunosuppressive tumor microenvironment (TME).

Methods
We p…

CXCL16-driven CD4+ T cells orchestrate immunosurveillance against MHC-I-deficient hepatocellular tumors

Background
Major histocompatibility complex class I (MHC)-I loss is a prevalent mechanism for immune evasion and resistance to immunotherapy. However, how MHC-I loss shapes the tumor microenvironment and influences immune cell interactions, ultimately…

Simplified perioperative serplulimab and chemotherapy for resectable squamous NSCLC: a phase II trial with biomarker analysis

Purpose
Squamous non-small cell lung cancer (sq-NSCLC) is a distinct subtype of NSCLC. This exploratory, phase II study investigated the feasibility and efficacy of a four-cycle perioperative regimen combining serplulimab with a taxane (paclitaxel or …

Phase 2 study of talabostat, a small molecule inhibitor of dipeptidyl peptidases (DPP), administered in combination with pembrolizumab in patients with small cell neuroendocrine prostate cancer

Background
Small cell neuroendocrine prostate cancer (SCNC) is a lethal subset of prostate cancer with limited treatment options. Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP 8/9) triggers the inflammasome to ale…

Humoral contributions to checkpoint blockade therapy

Checkpoint blockade immunotherapy has changed the landscape of cancer treatment for many types of malignancies, but it still does not work for all individuals and for all tumor types. Much work over the past decade has been dedicated to discerning wha…

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 …

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