mRNA vaccines seem to boost the effectiveness of an immune therapy for skin and lung cancer ― in an unexpected way.

Cancer-intrinsic genomic instability drives cytosolic DNA accumulation, triggering cGAS-STING immune signaling. Shim et al. review recent advances in cancer/cGAS-STING crosstalk, with a molecular-level focus on sources of cytosolic DNA and immunoregulatory mechanisms, including their therapeutic implications.

Nature Immunology - Brown and colleagues review the heterogeneity of mucosal antigen-presenting cells that orchestrate T cell immunity to intestinal antigens.

Di Meo et al. demonstrate that multiple myeloma relapses after CAR T cell therapy frequently express low BCMA levels by quantifying target antigen density on patient samples. SEMA4A regulates MM cell proliferation, migration, tissue infiltration, and osteoclast formation. SEMA4A-directed CAR T cells show superior activity in eradicating BCMAlow MM than BCMA-CAR T cells.

Abstract. Studies have identified a link between specific microbiome-derived bacteria and immune checkpoint blockade (ICB) efficacy. However, these species lack consistency across studies and their im...

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and develop...

Triple-negative breast cancer (TNBC) is characterized by high risks of relapse or metastatic disease. Mattavelli et al. identify a chemokine axis that recruits immunosuppressive monocytes to tumor-draining lymph nodes. By co-targeting this recruitment, the TNBC response to immune checkpoint blockade is augmented and metastasis to the lung is reduced.

Integrin CD103 mediates memory T cell tissue residency by binding E-cadherin-expressing epithelial cells, but why CD103 is also expressed on circulating naive CD8+ T cells has been unclear. Li et al. report that CD103 facilitates the interaction of naive CD8+ T cells with E-cadherin-expressing dendritic cells that in turn provide cytokine-mediated cues to promote their differentiation into memory-phenotype effector T cells.

Hesterberg et al. show that lymphoma provokes marked and rapid changes in young T cells that recapitulate the transcriptional, epigenetic, and senescent features manifest in aged T cells, including aging-associated alterations in inflammation, proteostasis, and iron homeostasis that also occur in other tissues of lymphoma-bearing individuals.

Rennen et al. provide methods to distinguish homeostatic from immunogenic mature cDC1s, based on lipid nanoparticle (LNP)-induced maturation. Only the uptake of TLR ligand- or mRNA-encapsulated LNPs i...

Nature - STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD

In this issue of Cancer Cell, Chen et al. identify DNASE1L3-expressing dendritic cells (DCs) as enhancers of anti-tumor immunity. By degrading neutrophil extracellular traps, these DCs promote CD8⁺ T cell infiltration into tumors and enhance checkpoint blockade efficacy, extending DNASE1L3’s known immune regulatory role to physical remodeling of the tumor microenvironment.

CD8+ T cell exclusion and dysfunction in the tumor microenvironment (TME) are among the most challenging obstacles for anti-PD-(L)1 therapy. Here, we …

Plasmacytoid dendritic cells are type 1 interferon (IFN-I)-producing antiviral specialists that have been shown to be able to differentiate into conventional dendritic cells. Here the authors show how...

Osorio et al. report a first-in-human study of intratumoral 2141-V11, an Fc-engineered CD40 agonistic antibody, showing it is safe and induces systemic and durable antitumor immunity in patients with ...

Rozalén et al. report that TIM3 in breast cancer drives a specific mechanism of immune escape during micrometastasis. TIM3+ tumor cells exhibit stemness/EMT features and promote immune-evasion by inducing immunosuppressive γδ T cells. TIM3 is a biomarker of poor outcome, and its blockade targets metastasis initiating cells during micrometastasis.

YouTube video by Francis Crick Institute

Tumor-associated neutrophils exhibit heterogeneity in breast cancer. Here, the authors identify a distinct precursor population (PreNeu) in estrogen receptor-positive tumors. PreNeu suppress homologou...

Ghisoni et al. profile the immune landscape of 697 ovarian cancers (OCs), identifying four immune phenotypes linked to prognosis and treatment response. The study demonstrates that BRCA-dependent TIL:...

Cole et al. report that adoptively transferred, tumor-specific Th17 cells engage host B cells and drive B cell proliferation and differentiation. These Th17 cells require B cells for sustained immunit...

Nature - Rapid extracellular antibody profiling reveals a contribution of autoantibodies to the effectiveness of checkpoint immunotherapy for cancer.

A newly identified bacterial strain (YB328) isolated from the faeces of patients who responded to immune checkpoint blockade therapies can promote antitumour immunity through the activation of tumour-...

Neutrophils actively induce tumour necrosis, driving vascular occlusion, pleomorphic necrosis and metastasis.

Neutrophils actively induce tumour necrosis, driving vascular occlusion, pleomorphic necrosis and metastasis.

Drug Discovery and Development covers strategies and technologies related to pharmaceutical research and development and drug formulation.

Disruption of dendritic cell (DC) interstitial motility in the tumour microenvironment promotes immune evasion, and enhancement of DC interstitial motility offers a route for DC-centric immunotherapy.

Tumor cell death shapes tumorigenesis and antitumor immunity in complex ways. Recently, Hänggi et al. revealed that necrotic-like death releases interleukin-1α (IL-1α), driving myeloid-mediated immunosuppression. Lamorte et al. demonstrated that medullary sinus macrophage (MSM) efferocytosis of apoptotic tumor cells activates the IL-33-regulatory T cell (Treg) axis, accelerating tumor growth. Blocking these pathways enhances the efficacy of cancer immunotherapy.

Tumor-induced systemic accumulation and polarization of neutrophils to an immunosuppressive phenotype is a potent driver of metastasis formation. Yet,…

Tumor cell death shapes tumorigenesis and antitumor immunity in complex ways. Recently, Hänggi et al. revealed that necrotic-like death releases interleukin-1α (IL-1α), driving myeloid-mediated immunosuppression. Lamorte et al. demonstrated that medullary sinus macrophage (MSM) efferocytosis of apoptotic tumor cells activates the IL-33-regulatory T cell (Treg) axis, accelerating tumor growth. Blocking these pathways enhances the efficacy of cancer immunotherapy.

Dendritic cells (DCs) induce infection-protective immune memory, which has yet to be exploited for cancer therapy. Here we show that type 1 DC vaccines quantitatively and qualitatively favors anti-tum...

Based on analysis of 2024 NIH funding data. Sums are totals of losses in funding to programs if indirect costs had been capped at 15%

Abstract. Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to...

The immune checkpoint receptor lymphocyte activation gene-3 (LAG3) inhibits T-cell activation and was recently validated as a target for cancer immunotherapy. Despite its emergence as a therapeutic t...

Nature Communications - In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors...

DC–T cell interactions during priming influence CD8+ T cell fate, and DCs subsequently sustain T cell responses against cancer.

Pooled genetic CRISPR screening is improved in complex models through leveraging internal controls.

Intermediate tumor-associated macrophages (TAMs) emerge first and give rise to two more differentiated TAM populations in pancreatic cancer.