2026
September
CD4 takes the lead: IL‑21 synergizes with KRAS inhibition for durable PDAC control
September 30, 2026
Pancreatic ductal adenocarcinoma (PDAC) has proven to be a challenge for immunotherapy treatment. KRAS inhibitors have shown efficacy in PDAC, but acquired resistance is common. In a recent publication in Cell, Qiang, Hoffman, Chun, et al. investigated whether combinations of KRAS inhibition with immunotherapy could improve long-term outcomes in murine PDAC models. The...
PLA2G2D: A new checkpoint lymph node macrophage
September 23, 2026
Tumor-draining lymph nodes (tdLNs) are critical sites for both antitumor immunity and tumor metastasis. To better understand what influences these events, van Krimpen and Huang et al. performed spatial proteogenomics studies on tdLNs from patients with melanoma. In addition to identifying a spatial neighborhood in the tdLN paracortex linked to poor prognosis, the...
Affinity matters for novel IL-2 variant that synergizes with other immunotherapies
September 16, 2026
Antitumor IL-2 treatment comes with challenges regarding toxicity and unintended Treg activation. To overcome these challenges, various approaches to engineer IL-2 variants (IL-2var) have been developed. In a recent Science Advances publication, Vormehr et al. reported preclinical data on an IL-2var delivered as mRNA encapsulated in lipid nanoparticles. The researchers aimed to identify...
Breaking down the mechanism of enfortumab vedotin
September 9, 2026
Enfortumab vedotin (marketed under the brand name Padcev) is an approved antibody–drug conjugate (ADC) that targets Nectin-4 on cancer cells and delivers a payload of microtubule-disrupting monomethyl auristatin E (MMAE) to tumor cells. In recent work, Olson and Liu et al. thoroughly investigated the mechanism of action of enfortumab vedotin, and identified direct...
Aire-ing out a tumor’s dirty laundry: manipulating tumoral AIRE to boost antitumor immunity
September 2, 2026
The autoimmune regulator (AIRE) transcription factor in medullary thymic epithelial cells (mTECs) is essential for the negative selection of autoreactive T cells in the thymus by inducing expression of peripheral tissue-specific antigens. Chen, Pulido, et al. hypothesized that AIRE expression in cancer cells may mimic this thymic process by establishing a “selfness” profile...
