Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort

Purpose
SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort…

Immunotherapy for rapid bone marrow conditioning and leukemia depletion that allows efficient hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure to treat hematopoietic disorders. Current bone marrow conditioning protocols create space for healthy donor stem cells by employing irradiation and/or chemotherapy, but carry se…

Targeting Annexin A2 to reactivate tumor-associated antigens presentation and relieve immune tolerance in liver cancer

Background
Tumor cells manipulate the tumor-associated antigens presentation to escape immune surveillance; however, the molecular mechanism is not exactly clear and the measure to intervene is missing.

Methods
Annexin A2 was knockout by the CRISPR-C…

SITC vision: Opportunities for deeper understanding of mechanisms of anti-tumor activity, toxicity, and resistance to optimize cancer immunotherapy

Cancer immunotherapy has radically changed the management of several malignancies, and dozens of agents have been approved in the past 15 years. While these advances have changed the field, many challenges lie ahead and must be addressed if we are to …

Mapping immune activity in HPV-negative head and neck squamous cell carcinoma: a spatial multiomics analysis

Background
Head and neck squamous cell carcinoma (HNSCC) exhibits low response rates to immunotherapies, with only about 15–25% of patients responding to monotherapy and 30–45% to combination therapy. This limited effectiveness is attribut…

Systematic identification and targeting of master regulator checkpoints (MRC) governing tumor microenvironment-mediated immune evasion

Abrogating the immunoevasive role of the tumor immune microenvironment (TIME) represents a critical yet still elusive challenge in cancer treatment. Progress in this area has been hampered by both technological limitations and incomplete understanding…

Ectopic expression of GDF15 in cancer-associated fibroblasts enhances melanoma immunosuppression via the GFRAL/RET cascade

Background
A key aspect of tumor biology is the involvement of cancer-associated fibroblasts (CAFs) in shaping the immunosuppressive microenvironment. However, the dynamic and complex key roles of CAFs in the melanoma immune microenvironment have not …

Potentiation of cancer immunogenicity by targeting PARP

A team of scientists led by Quigley Goa demonstrates that Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) can induce tumor cell death in a manner that allows immune cells to better recognize and attack the tumor. Specifically, PARPi are approved…

Bystander CAR-CD8+ T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody

Although bispecific antibody (BsAb) treatment is a valuable therapeutic option for post chimeric antigen receptor (CAR)-T cell therapy against relapsed/refractory large B-cell lymphoma, it remains to be clarified why it is still effective after intens…

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