Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade

Background
Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune re…

Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial

Background
Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an …

Glut3 overexpression improves environmental glucose uptake and antitumor efficacy of CAR-T cells in solid tumors

Background
Glucose deprivation inhibits T-cell metabolism and function. Glucose levels are low in the tumor microenvironment of solid tumors and insufficient glucose uptake limits the antitumor response of T cells. Furthermore, glucose restriction can…

Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors

Purpose
BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials and methods
This was a phase-I (NCT03444753) study that assessed the safet…

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review

Cancer immunotherapy—including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)—has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do…

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines

Background
Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a “cold” tumor type with poor i…

Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria

Background
Numerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, par…

Weal and woe of interleukin-18 in the T cell therapy of cancer

Chimeric antigen receptor (CAR) T cell therapy of solid cancer remains below expectations; adding cytokine help through IL-18 has shown remarkable efficacy in first clinical trials. As IL-18 is also a powerful driver of hyperinflammatory conditions, w…

CD93 blockade promotes effector T-cell infiltration and facilitates adoptive cell therapy in solid tumors

Background
Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a …

Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy

Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype characterized by aggressive clinical behavior and poor prognosis. The immune landscape associated with TNBC often reveals high immunogenicity. Therefore, immunotherapy, whic…

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