Banerjee et al. showed that Tim3 expression on tumor-infiltrating Tregs was required for their survival and suppressive function via Akt-FOXO1 signaling. Treg-specific Tim3 deletion in an MC38 model reduced tumor-infiltrating Tregs and CD25 expression, impaired Treg [...] bit.ly/4wxVfRo

Mallard de La Varende et al. showed that gut dysbiosis following treatment with antibiotics or antibiotic-associated species led to loss of secondary bile acids (BAs), increased tauro-conjugated primary BAs [...] bit.ly/4yRKlHO

Wang et al. evaluated a combination of nivolumab, ipilimumab, and mKRAS-VAX (six 21-mer synthetic long peptides targeting common KRAS mutations) in 13 heavily pretreated patients with MMRp/MSS metastatic colorectal cancer. bit.ly/3TvlZ6m

Hocine, Ganbaatar, and Amador-Molina et al. developed an IL7Rα (CD127)-targeted chimeric antigen receptor T cells and demonstrated their efficacy against T-ALL in vitro and in vivo, including in a patient-derived xenograft model using matched patient-derived CAR T cells. bit.ly/4fsl5Ab

Khalaj et al. performed a small molecule screen of FDA-approved compounds on CD11b+ tumor-associated microglia/macrophages isolated from patient GBM, and identified histone deacetylase (HDAC) inhibitors as enhancers of TAM phagocytosis. bit.ly/4fEdwW1

Muro and Wang et al. studied mechanisms by which lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines induce significantly higher levels of antigen-specific cytotoxic T cells and T cell-dependent antibodies compared to conventional adjuvant-based immunization. bit.ly/4h3W5QW

Cells responsible for TLS formation and maintenance. acir.org/weekly-dige...

cDC1s serve as architects for the formation and maintenance of tumoral TLSs

Mattiuz et al. assessed the role of dendritic cells in TLS formation and maintenance. Mature cDC1s were found to play essential roles, with TLS formation being dependent on maturation of cDC1s and their cross-presentation to T cells in the TDLN, followed by T cell recruitment to the tumor. Over time, maintenance of TLSs required the presence of cDC1s and cDC1 migration to CCR7 ligand-enriched stromal hubs, MHC-I and MHC-II antigen presentation to T cells, and CD40 signaling.

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Olea and Beede et al. identified Bacteroides rodentium and Bacteroides uniformis (found in mice and humans, respectively) as gut microbes that induced antitumor immunity and inhibited tumor growth in melanoma mouse models. bit.ly/44MPF1g

Kim et al. showed that anti-CTLA-4 efficacy in orthotopic murine glioblastoma (GBM) models was abolished by B cell deficiency and tdLN removal. In WT mice, anti-CTLA-4 increased B cell numbers and GC reactions in tdLNs, but not in the TIME [...] bit.ly/4pBDiPc

Zeng, Xu, and Wang et al. developed an optimized cancer vaccine platform comprising a novel LNP co-encapsulating tumor antigen mRNA and two STING agonists. bit.ly/4vMgON0

Wang et al. engineered an “all-in-one” cancer cell-derived vaccine (UniCVac) by co-expressing CIITA, NLRC5, CD80, and IL-2 in tumor cells to mimic professional APCs with both HLA-I and HLA-II antigen presentation, co-stimulation, and T cell growth signal. bit.ly/3Tc48Bn

Shen et al. developed COMPASS, an AI model that interprets pre-treatment tumor RNAseq data in the context of tumor-immune gene expression modules and maps them to predict ICB response. bit.ly/4yBe8Er

Investigating type 1 regulatory CD4+ T (Tr1) cells induced from conventional Foxp3-CD4+ T cells exposed to antigen-presenting tolerogenic DCs and IL-10, Cepika et al. used multiomic profiling and functional genomics to identify IRF4, BATF, and MAF as key transcription [...] bit.ly/4yGUVkT

CARM1 inactivation in cDC1s enhances their activation and antigen presentation, providing an avenue for enhanced immunotherapy acir.org/weekly-dige...

CARM1 inactivation in cDC1s completes the antitumor trifecta

Zhang et al. investigated the role of the CARM1 in cDC1s and found that while its effect on cDC1s in healthy tissues was minimal, inactivation of Carm1 in tumor cDC1s enhanced their activation and cross-presentation of tumor antigens, resulting in increased CD8+ T cell-mediated antitumor efficacy. Carm1 expression was found to be downregulated by type 1 IFN and TNFα, and upregulated by TGFβ via Smad2/3. CARM1 altered chromatin expression, with its loss leading to enhanced chromatin access at regions associated with NF-κB and AP-1 binding, which supported enhanced activation and antigen presentation. When used in combination with a neoantigen vaccine, inhibition of Carm1 enhanced antitumor responses.

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Marx, Teppert, and Marisch et al. showed retinoic acid-inducible gene-I (RIG-I), the cytoplasmic sensor of short dsRNA with uncapped 5’-triphosphate (3p-RNA), was expressed in human HCC samples and induced by IFN-I on cell lines. bit.ly/4w56D6W

Using single-cell multiomics and genetic models, Song and Kharel et al. showed that, paradoxically, both sustained A2AR expression under chronic antigen exposure and hypoxia, and complete loss of A2AR drive the transition of TCFhi memory-like progenitor (Tpro) cells [...] bit.ly/4ykaG0V

Nguyen et al. used single-cell RNAseq and multiplex IHC on paired primary thyroid carcinomas and metastatic lymph nodes (LNs) to define immune determinants of nodal colonization.  @cedarssinaicancer.bsky.social bit.ly/3RDaU2z

To enhance immunotherapy efficacy against escape variant clones, Ehara et al. combined MART-1 TCR-T cells with the ferroptosis inducer RSL3. IFNγ secreted by the TCR-T cells enhanced the susceptibility of melanoma cells to ferroptosis. bit.ly/44rzS81

Lelliott et al. showed that the CDK4/6 inhibitor trilaciclib enhanced the metabolic fitness of and cytotoxicity by human CD19 CAR-T cells while reducing their proliferation in vitro. @petermaccc.bsky.social bit.ly/456sQWk

Fumagalli et al. developed a focused CRISPR-knockout library targeting loss-of-function of 50 relevant genes to screen low-affinity EGFR CAR-T cells in an orthotopic human lung adenocarcinoma (A549) model. bit.ly/3T4lQXp @cnrsbiologie.bsky.social @inserm.fr @upcite.bsky.social

Heating up cold breast tumors 👉 bit.ly/44wKd2p.

Abascal et al. engineered FLT3L-secreting mouse cDC1s that retained APC and phagocytic ability in vitro. bit.ly/4baBExW

In an analysis of a multi-center trial involving 628 patients with high-risk melanoma receiving adjuvant pembrolizumab, Othus et al. identified optimal time cut-points for the first infusion of 1:18 pm for recurrence-free survival and 3:48 pm for overall survival (OS). bit.ly/4vujte8

Focused on improving transplantation tolerance, Ganchiku et al. evaluated a long-lived, high-affinity receptor binding IL-2 mutein (mIL-2) in multiple solid organ transplantation models. mIL-2 therapy [...] bit.ly/3SSlhzN  @harvardmed.bsky.social

Using immunopeptidomics and exome and transcriptome sequencing, Wang et al. analyzed 22 RCC samples and identified HLA-I-presented non-canonical tumor-specific antigens (TSA) derived from human endogenous retroviruses and long non-coding RNAs, with some shared across [...] bit.ly/3RprDGs

Graça et al. show that B cells are essential for CD8+ T cell effector response during chronic, but not acute, LCMV infection. bit.ly/4woD2VK

Suissa and Fidelle et al. performed targeted metabolomics to 4,336 plasma samples from 1,714 ICI-treated patients across 16 cohorts and trained an ML model that predicted 12‑month PFS, with [...] bit.ly/4gn7Kdj   @gustaveroussy.fr

Schmiechen et al. recently unraveled a complex web of escape mechanisms and immune interactions in pancreatic ductal adenocarcinoma. acir.org/weekly-dige...  @cfi-umn.bsky.social

Tregs versus Tconv: a battle over metastasis in PDA

Schmiechen et al. found that variants of PDA that escaped following PD-L1 blockade showed epigenetic silencing of Tap1 expression, which induced loss of IFNγ-inducible MHC-I and reduced tumor cell killing mediated by CD8+ T cell. Escape variants also had an increased capacity for metastasis, which was promoted by Tregs and their suppressive effect on conventional CD4+ T cells. Combination strategies involving restoring IFNγ-inducible MHC-I, targeting Tregs, and enhancing Tconv enabled more effective cancer immunotherapy, suggesting potentially targetable mechanisms to enhance immunotherapy in PDA.

acir.org

Using genetically engineered conditional mouse models and lentiviral-mediated somatic gene inactivation, Adler and Xu et al. developed models that allowed them to quantify immunoediting by evaluating fixed [...] bit.ly/4eTJ4qr

Rodriguez and Edinger et al. showed that pre-treatment with VLA-4-targeted, low-dose radiopharmaceutical therapy (RPT) using [67Cu] Cu-LLP2A enhanced GD2 or B7-H3 CAR T cell efficacy, resulting in significant tumor regression in xenogeneic, preclinical neuroblastoma models. bit.ly/4eREwAH