Ask about this productRelated genes to: Ly108 antibody
- Gene:
- SLAMF6 NIH gene
- Name:
- SLAM family member 6
- Previous symbol:
- -
- Synonyms:
- KALI, NTBA, KALIb, Ly108, SF2000, NTB-A, CD352
- Chromosome:
- 1q23.2-q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-10-29
- Date modifiied:
- 2018-02-13
Related products to: Ly108 antibody
Related articles to: Ly108 antibody
- Within days of exposure to chronic viral infections, activated CD8 T cells differentiate into Tcf1Slamf6Tim3 exhaustion-prone effector T (T) cells or self-renewing Tcf1Slamf6Tim3 precursor exhausted T (T) cells. Here we showed that early CD8 T cell fates were imprinted by forming subset-specific, self-associating chromatin hubs. Chromatin hub assembly coincided with effector or stemness gene induction and identified the transcription cofactors Id2 and Id3 as key regulators that promoted CD8 T and CD8 T cell fates, respectively. Id2 drove CD8 T cell specification by activating effector genes, while suppressing genes involved in exhaustion and stemness. In contrast, Id3-repressed effector genes but upregulated IL-7Rα and AhR, thereby maintaining the CD8 T cell pool. Mechanistically, Id2 and Id3 exhibited a distinct impact on the chromatin accessibility landscape in early CD8 T cells by engaging Runx3 and Tcf1 transcription factors along with E proteins. These findings indicated that reshaping chromatin architecture represents a critical means for specifying CD8 T cell fates and ensuring lineage stability. - Source: PubMed
Publication date: 2026/07/06
Hu WeiChen QingZhu ShaoqiHu Shengen ShawnYu HaiboPatel VanitaWang YingBadovinac Vladimir PZhang YiZang ChongzhiPeng WeiqunXue Hai-Hui - Mechanisms driving immunotherapy resistance in pancreatic cancer are poorly defined. We demonstrate that programmed death-ligand 1 immune checkpoint blockade promoted immune evasion by epigenetic () silencing, increasing selection of metastatic tumor variants with defective interferon-γ (IFN-γ)-inducible class I major histocompatibility complex (MHC-I) expression. Unleashing CD4 conventional T cells by regulatory T cell (T cell) depletion, transfer of tumor-reactive CD4 T cells, or anti-CTLA-4 prevented metastasis. Tumor-specific CD4 T cells adopted a TCF-1SLAMF6 progenitor state in lymph nodes and differentiated in tumors. Anti-CTLA-4 increased intratumoral accumulation of CD4 T cells with stemness and tissue residency features, reduced metastasis, and induced gene signatures correlated with improved patient outcomes. MHC-I restoration with anti-CTLA-4 prolonged survival in murine models. In patient tumors, T cells and CD4 T cells colocalized, and abundance correlated with survival. These findings identify targetable mechanisms of immune evasion and metastasis in immunotherapy-resistant cancer. - Source: PubMed
Publication date: 2026/06/26
Schmiechen Zoe CCruz-Hinojoza EduardoHilk Audrey LEllefson Madeline ATsai Alexander KDres Olivia MKang Liang-IGeuenich Michael JButler Jonah ZBurrack Adam LLarsen Brandon MHickok Grant HMiller Ebony ALonetree Cara-LinGaire AmritPandey RachanaNanda Hezkiel AChaudhury IndrajitCorbiere ThomasDileepan ThamotharampillaiShen Steven SCampbell Kieran RDeNardo David GStromnes Ingunn M - T cell exhaustion remains a significant barrier to effective adoptive cell therapy in solid tumors. Here, we demonstrate that in vitro treatment with the PI3Kδ inhibitor CAL-101 generates T cells with enhanced stemness and metabolic fitness. These cells show increased mitochondrial dependence and spare respiratory capacity while maintaining normal basal metabolism. Under chronic antigen stimulation, CAL-101-treated T cells, including human T cells, resist terminal exhaustion and maintain stem-like properties. Using single-cell RNA sequencing and spatial transcriptomics of B16 melanoma tumors, we found that CAL-101-treated T cells preferentially differentiate into progenitor exhausted T cells within the tumor microenvironment. These cells demonstrate enhanced tumor infiltration and upregulate the Cxcl10/Cxcr3 signaling axis. The tumor microenvironment of tumors containing CAL-101-treated T cells show reduced glycolysis, oxidative phosphorylation, and proliferation, while exhibiting increased proinflammatory signaling and decreased presence of immunosuppressive tumor-associated macrophages. Single-cell analysis reveals that the CAL-10-treated T cells concurrently increase oxidative phosphorylation, proliferation, and immune signaling pathways. Mechanistically, CAL-101-treated T cells maintain high expression of stemness-associated genes (Tcf7, Slamf6) while resisting expression of genes associated with terminal exhaustion (Tim3, Mt1/2). These findings reveal the mechanisms behind how PI3Kδ inhibition generates T cells capable of establishing and maintaining an antitumor immune response, suggesting a promising strategy for improving adoptive cell therapy outcomes in solid tumors. - Source: PubMed
Turnquist AlexandreaJavaid AzkaWilkins Owen MKolling Iv FredPioli Patricia APaulos Chrystal MRobert Frost HildrethUsherwood Edward J - The germinal center (GC) reaction requires tight regulation of B cell and T follicular helper (Tfh) cell interactions to ensure B cell expansion and antibody affinity maturation, while preventing oncogenesis. However, regulatory mechanisms fine-tuning B-T cell interactions within the GC to prevent aberrant activation and proliferation remain incompletely understood. Here, we identify Siglec-G, the mouse ortholog of human Siglec-10, as an immune checkpoint that restrains the GC by dampening B-T cell interactions. Selective and temporal ablation of Siglec-G on B cells after immunization triggers GC hyperplasia and enhanced plasma cell and antibody output. While Siglec-G is dispensable in B cell receptor (BCR)-mediated processes, it acts as an intrinsic inhibitory receptor of B-T cell interactions in the GC, ultimately limiting Myc and mTORC activation within positively selected GC B cells. interactions of Siglec-G and its glycan ligands on Tfh likely contribute in fine-tuning the strength of bidirectional signaling following contact between GC B cells and Tfh cells. This interaction is further reinforced by glycan remodeling that occurs in the GC, resulting in concurrent decreased in glycan ligands on GC B cells and increased in glycan ligands on Tfh. This augmented binding of Siglec-G/10 on Tfh is mainly due to the upregulation of α2-6 linked sialic acid ligands. Moreover, APEX2-based proximity labeling revealed several candidate Siglec-G/10 binding partners on T cells, including BTLA, CD6, and Slamf6, which are known negative regulators of Tfh cell activation. Taken together, our findings identified that Siglec-G acts as a GC checkpoint receptor, restricting B cell proliferation by tuning T cell help following B-T cell interactions. - Source: PubMed
Publication date: 2026/05/11
Enterina Jhon RLin Sung-YaoLuna-Dulcey LianySarkar SusmitaSchmidt Edward NJame-Chenarboo ZeinabChisholm KennedyHaq Arbab UlLuo ShuLaurent Chris D StAtaei TheoGiuliani FabrizioJulien OlivierMacauley Matthew S - T helper (Th) and T follicular helper (Tfh) cells support cellular and humoral immunity, respectively. How activated CD4 T cells commit to these fates remains unclear. Using a mouse vaccination model, we traced endogenous, polyclonal CD4 T cells during bifurcation into Th1 and Tfh lineages. We found that Th1 and Tfh cells originate from shared, highly proliferative TCF1SLAMF6PD-1 precursor clones that co-express Th1- and Tfh-related transcription factors and chemokine receptors, including T-bet, BCL6, CXCR3, and CXCR5. The generation of common Th1/Tfh precursors from naive CD4 T cells requires CD28 costimulation but occurs independently of CD40, ICOS, and interaction with type 1 conventional dendritic cells (cDC1s) or B cells. Lineage commitment subsequently diverges: differentiation into Th1 cells relies on CD40 costimulation and cDC1s, whereas differentiation into Tfh cells requires ICOS costimulation and B cells. Activated CD4 T cells thus give rise to a common Th1/Tfh precursor whose fate depends on interactions with distinct antigen-presenting cells. - Source: PubMed
Publication date: 2026/04/21
Bosma Douwe M TBusselaar JuliaStaal Mo Dde Koning MylèneReljić MirnaLei Xinde Wit TomXiao YanlingBorst JannieSalerno Fiamma