🗺️ Using an atlas to learn where not to go - human DC atlas reveals inhibitory cDC1 variant associated with poor outcome doi.org/10.1038/s415...

👏 A few good Mon(omers) - IL-10 monomers linked to anti-PD-1 are safe and exhibit good anti-tumor activity doi.org/10.1016/j.xc...

👉 Remodeling the TME from within- A pipeline to target Knock-In of T cell directing cytokines to mutation sites in personal genomes doi.org/10.1038/s414...

🤔 When Tregs aren't Tregs: A unique IL-10+ Treg population in CRC is tumor-inhibitory biorxiv.org/content/...

Motmaen et al. developed a structure-based deep learning strategy (ADAPT) for pMHC binder design that leverages AlphaFold2 for conformational sampling, ProteinMPNN for CDR design, and iterative re-docking and a genetic algorithm for interface amino acid refinement. bit.ly/3YEvAHb

Giovannoni, Strathdee, and Akl et al. engineered an HSV-1 platform for GBM viroimmunotherapy. Incorporation of EGFR- or integrin-binding gD variants expanded GBM tropism, fusogenic mutations enhanced intratumoral spread, and miRNA attenuation protected healthy CNS tissue. bit.ly/490r2Qe  

Matsuura et al. showed that PGE2 in the TME induced tumor-infiltrating Treg (TI-Treg) signature genes through the EP2/EP4–cAMP–PKA signaling axis in both induced and naturally occurring Tregs, enhancing their suppressive potency. bit.ly/4s3milI

Stewart et al. used mRNA engineering to generate DC-25 – an allogeneic, off-the-shelf, mesenchymal stem cell (MSC)-based therapy for cancer immunotherapy and autoimmunity. bit.ly/4pPMr6a  

Ming et al. generated oil-water emulsions stabilized by alum particles (ASPEs) to mechanically activate DCs. Increasing alum crystallinity increased ASPE interfacial stiffness, in turn increasing DC contact area, membrane tension, and internalization, leading to [...] bit.ly/493XXnj

Gammelgaard ‍‍and Ehmsen et al. showed, in a phase 1B trial in patients with locally advanced or metastatic TNBC, good safety and tolerability to chemotherapy plus ex vivo-primed autologous lymphoid effector cells (polyclonal CD4+ and CD8+ T and NK) produced from [...] acir.org/journal-art...

Armoring CAR-T for neutrophil engagement. bit.ly/3N4Zkuk

Ibanez-Molero and Veldman et al. isolated heterotypic clusters of CD8+ T cells with tumor cells and antigen-presenting cells (APCs) from melanoma metastases, revealing stable conjugates normally excluded by single-cell gating. bit.ly/440mnfK  

Weng et al. focused on unexplored mechanisms that contribute to T cell exhaustion. They observed that CD47, upregulated on human and murine tumor-infiltrating exhausted CD8+ T cells [...] bit.ly/3MgShyo  

Li et al. generated CAR-NKT cells by transducing cord blood HSPCs with an anti-mesothelin CAR, the iNKT TCR, and sIL-15, prior to a 6-week NKT differentiation protocol with high purity and yield. bit.ly/3KcEoRj

Investigating neuroblastoma, Giudice et al. found that in both mice and patient samples, tumor-derived extracellular vesicles (EVs) displayed CAR T cell target antigens GPC2 and GD2, with minimal expression [...] bit.ly/48MUaLT

Song, Lu, and Shi et al. demonstrated that an MHC-II restricted neoantigen vaccine (M44) increased inflammatory signaling within the TME, enhanced CD4+ and CD8+ T cell infiltration, and reduced tumor growth [...] bit.ly/4rFb8n6

Sergeeva and Jin et al. developed the EVOLVE trispecific T cell engager (TCE) platform, comprising a tumor antigen-targeting domain, an affinity-attenuated CD3 agonist (optimized to increase T cell viability and [...] bit.ly/48xEnPV

Fueling CAR with IL-9 bit.ly/4ox164C

Xiang et al. integrated whole-genome, transcriptomics, and MHC-I immunopeptidomics analyses to identify tumor-specific antigens from non-coding regions in colorectal cancer samples. bit.ly/48epAJO

Focused on key TME regulators that control cDC1 cross-presentation, Xie et al. found that cDC1-expressed Ms4a7 was critical for effective CD8+ T cell-mediated antitumor immunity in mouse models. bit.ly/3XlHPbf

Damle and Carter et al. integrated spatial proteomics, tissue microarray, multiplex immunofluorescence imaging, and transcriptomics data from highly desmoplastic fibrolamellar carcinoma, and [...] bit.ly/4ohk276  

Taking advantage of low IL-9R expression in normal tissues, Jiang et al. engineered T cells with wild-type IL-9R. bit.ly/4prS4Xo  

Baiu et al. showed that CD4+ invariant natural killer T cells (iNKT) and autologous or allogeneic monocyte-derived DCs formed stable complexes, with enhanced expression of MHC I, 4-1BBL, OX40L, and IL-15Ra in DCs, and CD70 in iNKT cells. bit.ly/3XjyUXO

Dong et al. encoded the ICD-inducing protein 4HB in LNPs optimized for tumor cell specificity and hepatocyte avoidance, which significantly improved tumor cargo expression compared to a clinical control LNP (>90% vs. ~25%). bit.ly/4p42Nrq

New ‘al-MiTE-y’ TAM reprogramming strategy bit.ly/485QEMs

🆕 The (new) T cell vocabulary: A consensus, modular framework to rationalize T cell description doi.org/10.1038/s415...

Marabelle highlighted that the prognostic value of biomarkers is treatment-dependent, citing the Philadelphia chromosome as a poor prognostic marker for leukemia before imatinib became available, but a key therapeutic target after. #SITC25 bit.ly/3LLunuM

⏰ Is it time to learn? Mining the available data on neoepitopes to understand and predict link.springer.com/ar...

👉 An inside job for retroviruses: In vivo delivery of stimulatory cargos to Ts of interest by peptide:MHC-targeted retroviruses science.org/doi/10.1...

Moran Amit finished his #SITC25 talk by summarizing that nerve injury, often caused by perineural invasion, drives an immunosuppressive microenvironment, causing resistance to anti-PD-1. bit.ly/3LLunuM

🔎 Stepping back to get a closer look: Ecotypes of immune cells and cell states across cancer types links to survival doi.org/10.1038/s414...

Our #SITC25 recap is out today! Check out the standout presentations and insights from top institutions and speakers: bit.ly/3LLunuM#SITC25

Gao, He, and Wang et al. show that Trilaciclib (CDK4/6 inhibitor) inhibits NSCLC progression in immunocompetent, but not immunodeficient, mice bearing s.c. LLC and CMT167 tumors. bit.ly/3WUHX19

Heyden et al. show that chromatin organizer SATB1 is enriched in TPEX cells and limits exhausted CD8+ T cell expansion and effector differentiation in chronic infection and cancer, while maintaining functionality. bit.ly/47Dwnhc   @thedohertyinst.bsky.social  @unimelb.bsky.social

Bachem, Clarke and Kong et al. studied the role of microbiota-derived short chain fatty acids (SCFAs) in an orthotopic melanoma model, revealing a direct link between melanoma control, CD8+ T cell differentiation [...] bit.ly/4p4v40r   @thedohertyinst.bsky.social  @unimelb.bsky.social

To overcome the immunosuppressive TME in glioblastoma, Lunavat and Nieland et al. identified the cell types involved in tumor control following i.t. IL-12 therapy in mice. bit.ly/3XmwCXQ   @harvardmed.bsky.social

Giguelay and Maschmeyer et al. detected only minor differences in the PBMC immune cell composition of 17 cancer patients receiving ICI therapy, 8 with and 9 without severe neurological immune-related adverse events (n-irAEs). bit.ly/49MOC4X  @leifludwig.bsky.social

Zhang et al employed cytotoxic B-elemene (ELE)-treated dying cancer cells (DCCs) as an immunogenic cell source within a sprayable fibrin hydrogel (with additional ELE). bit.ly/3JKRBk4

Gujar and Cui et al. recently developed N17350 – a cancer-specific therapeutic elastase t – and tested it in a wide range of preclinical models bit.ly/4p8h9GN  

Wang et al. generated αTIGIT-IL2, an immunocytokine comprising IL-2 and an anti-TIGIT scFv fused to a human IgG1Fc. bit.ly/3Lull4Z

Khelil et al. demonstrated that SALL4 is overexpressed in multiple tumor types, including primary colorectal cancers and paired liver metastasis, but is silenced in almost all adult tissues. bit.ly/43dpgJD   @gustaveroussy.fr

Tan et al. reported clinical outcomes and translational analyses of patients with early-stage DNA mismatch repair-proficient colon cancer from the phase II NICHE trial. bit.ly/3LoDYHJ   @myriamchalabi.bsky.social

Compared to TCRs, CARs have poorer recruitment of proximal signaling molecules and antigen (Ag) sensitivity. bit.ly/3LgQLvQ   @stanfordmedicine.bsky.social

Sasaki et al. addressed the toxicity of IL-12 that has caused dose-limiting immune-related adverse events (irAEs). bit.ly/43IbhM4  @ko1ssk.bsky.social

Takahashi et al. established a multi-site murine tumor model system for temporal tracking of CD8+ T cell phenotypes and clonal dynamics, identifying a “precursor exhausted” PD-1+Ly108+ population as a driver of clonal expansion. bit.ly/3JFFN2f

COVID-19 vaccines aid cancer treatment bit.ly/4nD1cqI   @mdanderson.bsky.social

Using spatial multiomics, Cakmak et al. profiled 642 adult-type diffuse gliomas and identified tertiary lymphoid structures (TLSs) in 15% of the tumors. bit.ly/3JABEN5  @loewe-fci.bsky.social  @imkeller.bsky.social

Across various soluble and cell-bound signals, Avanessian and van den Bijgaart et al. identified IL-2 and IL-15 to be uniquely capable of inducing Flt3L production by immunomodulatory NK cells. bit.ly/3JBJmGP  @fredhutch.org

Ghasemi et al. engineered DC progenitors expressing IL-12 and a non-signaling receptor (EVIR) targeting GD2, which promoted uptake of GD2+ cancer cells and their EVs. bit.ly/47dNbuS

Afratis et al. focused on disrupting key extracellular matrix (ECM) pathways in the TME by engineering dual-targeting decoys that simultaneously targeted the collagen cross-linking enzyme LOX [...] bit.ly/4oILnQq   @weizmanninstitute.bsky.social