We’ve rounded up 18 must-see talks from #CICON25. Catch the highlights in our digest. 👉 bit.ly/4pEy04Y#CICON25

CTNNB1S37F is a driver mutation found across solid tumors. Using an HLA+ cell line transduced with CTNNB1S37F, Eggebø et al. used MS to identify two HLA-bound neopeptides that were also expressed naturally on CTNNB1S37F+ tumor cells. bit.ly/4gtsj5T  

Abrantes and Forcados et al. generated and characterized AM52.1, a pan-carcinoma antibody with exclusive specificity for a truncated O-glycan structure Sialyl-Tn antigen (STn), which is found on various epithelial tumors [...] bit.ly/42uU73N  

Last week, our team had the privilege of attending CICON 2025 in Utrecht! We’re putting together a digest of highlights from selected talks dropping on September 24. Stay tuned for key takeaways you won’t want to miss. #CICON25 #CancerImmunotherapy

Yang, Wang, and Fu et al. profiled 15 responding and 21 non-responding metastatic melanoma tumors and identified 14 cell types and 55 subtypes, including a mature dendritic cell subtype enriched in immunoregulatory [...] bit.ly/3Vm6mvL   @manoliskellis.bsky.social

Lu and Luo et al. performed CRISPR screens in primary macrophages and identified lactic acid, PGE2, and GM-CSF as tumor-derived modulators of TAM polarization. bit.ly/3K4pbRT

Using scRNAseq data from patients with ICI-treated melanoma, Bae et al. profiled conventional CD4+ T cells (excluding Tregs and proliferative cells) at the lesion level. bit.ly/4nFmqVI

TCR KO supports allogeneic CAR T cells, but also results in CD3 antigen loss from the cell surface. bit.ly/3VTVyFj  

New driver of T cell dysfunction in tumors uncovered 👉 bit.ly/4mgJAQV  @delgoffelab.bsky.social

Using a sequential anchored transcription factor screen, Henriques-Oliveira, Altman, and Kurochkin et al. identified two transcription factor triads: PU.1, IRF4, and PRDM1 as inducers of cells similar to type 2 conventional DCs, and [...] bit.ly/4pbCGiO

Sidiropoulos et al. report state-of-the-art spatial genomics and proteomic profiling of PDAC tumors and tumor-adjacent lymph nodes from patients treated with GVAX and anti-PD-1 alone or in combination with [...] bit.ly/4m1SvFM  @ltkagohara.bsky.social‬  @jhu.edu‬

Xing, Zhou, and Wang et al. demonstrated the role of CD103+CD8+ T cells in protection against breast cancer lung metastasis. bit.ly/46m1HA4

Hong et al. investigated sac-TMT, a TROP2-targeted antibody–drug conjugate, in combination with tagitanlimab (anti-PD-L1) as a first-line therapy in advanced NSCLC without actionable genomic alterations. bit.ly/4g3d6bo

Focusing on antigenic heterogeneity and antigen loss in solid tumors, Xiao, Wang, and He et al. engineered T cells to express FLT3L and XCL1 (FX). bit.ly/4pnTUJV

Singer and Pabón et al. developed a Salmonella typhimurium bacterial platform that delivered non-spreading, self-replicating viral RNA, even into cell types beyond the virus’s natural tropism. bit.ly/3I48J3i ‪@columbiauniversity.bsky.social‬

Azevedo et al. found that aberrant glycosylation drives T cell exhaustion, starting in early tumors ‪@delgoffelab.bsky.social‬. Read about it here: acir.org/weekly-dige...

Researchers showed that the bark-derived, saponin-based adjuvant Matrix-M® (M®; used in COVID-19 and malaria vaccines) – comprising Matrix-A (A) and, to a lesser extent, Matrix-C (C) nanoparticles – colocalized with antigens in lysosomes [...] bit.ly/47hu03Q  ‪@novavax.bsky.social‬

Researchers engineered an inhalable small extracellular vesicle (sEV) loaded with mesothelin-specific CAR mRNA (CARmRNA@aCD206 sEVs) to generate CAR-Ms in situ. bit.ly/4oUOKET

Biederstadt and Basar et al. developed a genome-wide CRISPR screen platform for primary human NK cells, and identified MED12, ARIH2, and CCNC as critical regulators of NK cell function under repeated tumor [...] bit.ly/4oRiO4l   ‪@mdanderson.bsky.social‬

Zhao et al. engineered a chimera of an IL-2 receptor domain linked to the transmembrane and intracellular domains of diverse, orthogonal (o) cytokine receptors to explore novel JAK/STAT outputs in T cells bit.ly/4n4mMEV   @stanford.edu‬

Wang et al. focused on improving the potency and specificity of mAbs targeting cancer- and infection-associated carbohydrates bit.ly/3Vnk29G   @cornelluniversity.bsky.social‬

Deletion of the glycan regulator SPPL3 improved allo-CAR-T fitness by reducing T cell, NK cell, and FasL-mediated killing bit.ly/45S4zDD

Following poor clinical trial outcomes, Aznar and Good et al. explored mechanisms of CAR-T resistance in solid tumors. Read our digest 👉 bit.ly/47NvCCn

Using mouse models of HNSCC and melanoma, Restaino, Ahmadi, and Eichwald et al. showed reduced growth of small extracellular vesicle (sEV)-deficient tumor cells in nociceptor neuron-ablated mice. bit.ly/4fLsPeV  

Ma et al. demonstrated that succinate promoted CD8+ T cell mitochondrial fitness and enhanced antitumor immunity. bit.ly/476EvXw

Li et al. identified broad expression of NKR ligands on ovarian tumor cells, motivating the application of allogeneic, IL-15+ CAR NKT cells, which were effective in CAR antigen+/- xenograft models, and exhibited strong [...] bit.ly/41f9YmI  

14 patients with B cell cancers and 1 with autoimmune disease were treated with allogeneic anti-CD19 CAR T cells edited for immune evasion (TRAC/B2M/CIITA KD + CD47 overexpression), following lymphodepletion. bit.ly/3UXipzD  

Tiwary et al. focused on improving dendritic cell (DC) cancer vaccine effectiveness using a transgenic mouse model (FAT-1) generating high omega-3/omega-6 lipid ratios. bit.ly/45JwS70

Arai et al. demonstrated that the EML4-ALK fusion gene created a myeloid cell-driven immunosuppressive TME. bit.ly/4mqOXhu  

An agonist anti-CD40 with enhanced binding to FcγRIIB showed early promise in a small cohort of patients with metastatic melanoma. Read our digest here 👉 bit.ly/4nc91nR  @juanosoriomd.bsky.social‬  @mskcancercenter.bsky.social‬

Pinho et al. detected circulating tumor-reactive CD8+ T cell responses in the blood of patients with early-stage HR+ breast cancer by ex vivo stimulation. bit.ly/3V3IWLi  

Xie et al. found that the probiotic Clostridium butyricum was both depleted in patients with CRC and potentiated anti-PD-1 efficacy in mouse models of CRC (orthotopic MSI-H and MSS). bit.ly/45r1DyV

🤔 Just thinking about immunology - Oh wait! Thinking (well, at least neuronal activity) and immunology overlap. A review doi.org/10.1038/s415...

🔆 Shedding more light on the dark proteome - a new tool to identify non-canonical proteins doi.org/10.1038/s415...

Using orthotopic 4MOSC murine models, Saddawi-Konefka et al. showed that the preferential migration of immune cells to the tumor-draining sentinel lymph nodes (SLNs) creates a unique immunologic niche [...] bit.ly/4mCRRz9   ‪@ucsdmedschool.bsky.social‬

In mice dermally infected with OVA-expressing vaccinia virus and administered OT-I cells, PD-1+ cells constituted the majority of skin OT-I Trms both during infection and after clearance. bit.ly/4lrqPdi  @weillcornell.bsky.social‬

Dai, Aizenbud, and Qin et al. profiled the reactivities of autoantibodies (AAbs) from healthy donors and ICB-treated patients. bit.ly/45OZ2i8   @yaleschoolofmed.bsky.social‬  @fredhutch.bsky.social‬

Demonstrating broader use of their HapImmune platform, Maso and Rajak et al. developed antibodies targeting novel “neoantigen” peptides derived from KRAS(G12C) covalently bound to [...] bit.ly/4mLmKlf  

Migrating vs resident T cells for antitumor efficacy. Read our summary: bit.ly/413AiQA  @thedohertyinst.bsky.social‬  ‪@rauschlisa.bsky.social‬

Householder et al. used RFdiffusion and ProteinMPNN to de novo design an α-helical TCR mimic (TCRm) specific for an NY-ESO-1 peptide on HLA:A*02. bit.ly/4myrpa4  

Johansen, Wolff, Scapolo, et al. used a known crystal structure, RFdiffusion, and other generative models to rapidly de novo design high-affinity minibinders (miBds) targeting the [...] bit.ly/3J1yoK8 ‪@mfernandezquintero.bsky.social‬  ‪@scripps.edu‬  ‪@tpjenkins.bsky.social‬

⭕ How to leverage a tumor - a review on the emerging excitement about neoadjuvant immunotherapy doi.org/10.1038/s430...

🐥 The new kids on the block Rock! - Newly emergent genes are tied to tumorigenesis and may be good neoantigens doi.org/10.1016/j.xg...

Ahn et al. showed in vitro (using human PBMCs) and in mice that IL-10 suppressed IL-2 induction of CRS-associated cytokines by suppressing TNFα production while potentiating IL-2-mediated antitumor activities. bit.ly/3UPCMhO

Murer et al. engineered ANV600 – a novel bispecific antibody–cytokine fusion protein that binds to a non-blocking PD-1 epitope and targets IL-2 to PD-1-expressing cells, without interfering with concomitant anti-PD-1 therapy. bit.ly/46EZUH7

Huang, Theelen, and Belcaid et al. report the immunomodulatory effects of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in patients with metastatic NSCLC based on a phase 2 trial. bit.ly/4omCD32  ‪@johnshopkinsmmi.bsky.social‬  ‪@nkinl.bsky.social‬

Gong and Luo et al. developed the Cancer Immunology Data Engine (CIDE) using 90 omics datasets with 8,575 profiles from 5,957 patients with 17 solid tumor types. bit.ly/4mtCGID

A novel pipeline could be used to design binder proteins that mimic the TCR in targeting of peptides bound to MHCI molecules 👉 bit.ly/453lmo2

Zabala-Peñafiel, Gonzalez-Lombana et al. showed that mice vaccinated s.c. with LNPs containing mRNA encoding leishmanial PEPCK antigen generated specific dLN and splenic Th1 and T follicular helper cells [...] bit.ly/3GMQ4sk

We cover 3-5 cancer research conferences a year distilling standout talks and fresh insights. Thanks to our readers for caring. And to the speakers: your work shines even brighter in our newsletter 💙 #CancerScience #ConferenceCoverage #CancerResearch #ScienceCommunication bit.ly/3SY9M6V