2024
July
TAMing immunotherapy resistance by targeting TIM3+VISTA+ macrophages
July 31, 2024
Immunosuppression by tumor-associated macrophages (TAMs) is thought to be one of the resistance mechanisms limiting the efficacy of immune checkpoint blockade (ICB) in cancer. In a recent publication in Science Advances, Vanmeerbeek et al. analyzed a newly described TAM subset present in unresponsive tumors, and assessed ways to target this population. The researchers...
First signs of clinical efficacy for personalized TCR-engineered T cells
July 24, 2024
Targeting neoantigens using adoptive cell therapy (ACT) has been a promising approach to personalized cancer therapy, but isolating, identifying, and expanding relevant and high-quality T cells remains a challenge. In ongoing efforts to improve neoantigen-targeted ACT, Parkhurst et al. is conducting an ongoing phase 2 single-arm trial of TCR-engineered autologous peripheral blood lymphocytes...
Timing is everything when combining radiation and immunotherapy
July 17, 2024
Even though the combination of radiotherapy and immune checkpoint blockade (ICB) has great potential to work synergistically, clinical efficacy has been limited. Irradiation of the draining lymph nodes (dLNs) to target metastases might be to blame for this, as these are essential places for antigen presentation and priming of T cells, needed for...
A closer look at inflammation suggests new treatment approach for PDAC
July 10, 2024
Pancreatic ductal adenocarcinoma (PDAC) remains refractory to immunotherapy due to a compromised tumor immune microenvironment (TIME) with dysfunctional T cells, suppressive myeloid and regulatory T cells (Tregs), and a sparsity of neoantigens and antigen-presenting cells. Patients with a history of chronic pancreatitis have an increased risk of developing PDAC, and progression of pancreatic...
JAK-ing up ICB responses with JAK inhibitors
July 3, 2024
One of the main outstanding issues for cancer immunotherapy is how to improve the efficacy of immune checkpoint blockade (ICB) in subsets of patients who currently do not benefit. Two recent back-to-back publications in Science tackled this issue by combining ICB with JAK inhibition. Zak, Pratumchai, Marro, et al. performed preclinical and clinical...
