The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway has a crucial role in detecting tumour-derived DNA, whether the pathway is generated spontaneously or induced therapeutically. Activation of the cGAS-STING pathway triggers type I interferon signalling and pro-inflammatory responses in both tumour and immune cells, establishing a delicate balance between pathological inflammation and protective immune responses. Although preclinical studies have highlighted the promise of targeting the cGAS-STING pathway to enhance antitumour immunotherapy, clinical results have fallen short of expectations. In this Review, we outline key advances in understanding the tumour-promoting and tumour-suppressive effects mediated by the cGAS-STING pathway and discuss opportunities and challenges for its integration into future cancer immunotherapy.

LAG3 is a critical inhibitory receptor that is highly enriched on exhausted T cells within the tumor microenvironment (TME), where it acts as a key driver of T-cell exhaustion—an archetypal barrier to robust antitumor immunity. In a colon cancer model, LAG3+CD8+ tumor-infiltrating lymphocytes (TILs) constitute the predominant type of tumor-specific T cells but exhibit defective IL2 signaling. To address whether exogenous IL2 replenishment unpins their dysfunction, we engineered LAG3-LaIL2 (low-affinity IL2), a fusion protein that selectively delivers IL2 to LAG3+CD8+ TILs. LAG3-LaIL2 expanded pre-exhausted tumor-specific CD8+ T cells, reprogrammed their exhaustion trajectory toward an intermediate effector state, and prevented terminal exhaustion, leading to tumor regression and prolonged survival in mice. Mechanistically, LAG3-LaIL2 restored IL2R-JAK3-STAT5 signaling by upregulating the high-affinity IL2 receptor subunit CD122, thereby restoring TIL functionality. Furthermore, LAG3-LaIL2 amplified tumor-specific effector and memory T cells in draining lymph nodes, enabling systemic antitumor immunity against distal tumors and preventing tumor recurrence. Collectively, our findings identify LAG3-LaIL2 as a precision immunotherapy that specifically targets exhausted TILs while restricting IL2 exposure to nontarget cells, thereby enhancing both the efficacy and safety of this approach. This approach provides a translatable strategy to overcome T-cell exhaustion in solid tumors and represents a promising avenue to improve clinical outcomes in cancer patients.

Immune-cold tumors fail to respond to immunotherapy due to insufficient lymphocyte infiltration within the tumor tissue. Increasing the objective response rate remains an urgent challenge. Here, we report the development of a monoclonal antibody (6C5) that specifically targets the membrane-proximal epitope of the receptor tyrosine kinase AXL and modulates antitumor immunity. Unlike traditional membrane-distal AXL antibodies, which suppress tumor growth primarily by blocking AXL signaling, 6C5 significantly enhanced innate immune sensing by promoting macrophage-mediated antigen uptake and type I interferon production. These effects further activated dendritic cells and increased CD8+ T-cell infiltration and effector function, thereby reshaping the tumor microenvironment. However, AXL antibody treatment concurrently induced a suppressive subset of PD-1hiFoxp3-CD4+ T cells. These cells displayed a transcriptomic profile resembling that of Tregs, characterized by elevated expression of immune checkpoint molecules (including PD-1 and CTLA4), reduced IL-2 production, and increased IL-2 receptor expression, thereby attenuating antitumor immune responses. The combination of 6C5 with dual immune checkpoint blockade (anti-PD-1 plus anti-CTLA-4) or a PD-1-targeted IL-2 fusion protein therapy mitigated this immunosuppression, resulting in potent tumor regression and durable immune memory. Our findings demonstrate that a membrane-proximal AXL-targeting antibody effectively converts the immune-cold tumor microenvironment, overcoming resistance to both conventional and next-generation immune checkpoint inhibitors.

Adoptive cell therapy (ACT) against solid tumors is constrained by tumor heterogeneity, immunosuppressive microenvironments, and insufficient T cell potency and persistence. Although IL-12 has long been recognized as a potent enhancer of T-cell immunity, its clinical application has been hindered by systemic toxicity and the lack of a strategy to harness its benefits without chronic exposure. Here, we show that ex vivo IL-12 preconditioning programs tumor-specific T cells with increased antigen sensitivity, yielding superior antitumor activity compared with IL-7/IL-15. Systemic delivery of Pro-IL-12 further rejuvenates exhausted CD8+ tumor-infiltrating lymphocytes (TILs) by restoring IL-2 hypersensitivity, sustaining persistence, and strengthening effector machinery. When combined with ACT, a single dose of Pro-IL-12 reinstated IFN-γ production in exhausted TILs and doubled intratumoral T-cell accumulation via upregulation of IL-2Rα and increased IL-2 sensitivity. Pro-IL-12 markedly improved therapeutic outcomes, inducing durable complete tumor regression, promoting antigen spreading, and establishing long-term immune memory that prevented relapse from antigen-loss tumor. Across multiple xenograft models, including pancreatic cancer, lymphoma and triple negative breast cancer, distinct human CAR-T products paired with Pro-IL-12 enhanced tumor eradication without cytokine release syndrome. Together, these findings establish precision delivery of IL-12 as a translatable strategy that harnesses known IL-12 biology to achieve robust antitumor efficacy without systemic toxicity.

Tumor infiltrating T cells (TIL) are key players in the anti-tumor immune response. However, chronic exposure to tumor-derived antigens drives the differentiation into 'exhausted' TILs. Whether intratumoral dendritic cells (DC) can mitigate TILs exhaustion and maintain function is unclear. Here, we develop a bispecific DC-T cell engager (BiDT), consisting of an anti-TIM3-IFN fusion protein, and demonstrate that, in preclinical mouse tumor models, this engager simultaneously targets TIM3 on exhausted TILs and activates DCs via the IFNAR receptor. Mechanistically, BiDT reactivates exhausted TIM3+TILs by preventing apoptosis through increased Bcl-2 expression and enhances DC function to reactivate T cells via IL-2 signalling and co-stimulatory CD80/86-CD28 interactions within the tumor microenvironment. Finally, to mitigate IFNα-induced toxicity, we engineer a Pro-BiDT engager featuring a pro-IFNα and report potent antitumor activity with reduced systemic toxicity. Thus, by bridging DC-T cells together, BiDT treatment enhances the critical communication pathways and cellular circuits necessary for effective anti-tumor immunity.

Immune cell engagers have emerged as a powerful class of multi-specific therapeutics that redirect immune effector cells toward tumor cells to induce targeted cytotoxicity. Among these, T cell engagers (TCEs) represent the most clinically advanced platform, with multiple approved agents demonstrating substantial efficacy in hematologic malignancies. However, their broader application remains limited by systemic toxicities, antigen heterogeneity, and reduced efficacy in solid tumors. To address these challenges, next-generation TCEs are being engineered with improved selectivity, and optimized signaling properties. In parallel, increasing attention has shifted toward engaging alternative immune effectors, including γδ T cells, natural killer cells, and myeloid populations, which provide complementary mechanisms of tumor recognition and immune modulation. In this Review, we summarize the biological principles underlying T or other immune cell engagers, highlight emerging alternative platforms, and discuss evolving engineering strategies that are shaping the future of programmable cancer immunotherapy.

Abstract Cold tumors evade immunotherapy through limiting T cell priming inside draining LN or infiltration into TME. Here, we have developed sequential strategies to overcome the limitation. Firstly, we have developed new mRNA vaccine expressing membrane cytokines with shared or mutated antigens to more and better prime tumor specific T cells (TST) without toxicity. Secondly, we generated tetramer forms of NGR that fusing into Fc-pro-IL2 that selectively targeted CD13 enriched on TME for more IL-2 to rejuvenate dysfunctional T cells. Unexpectedly, cis-delivery of IL-2 on CD13 on tumor vessels can bridge the cross-talk between tumor vessels and TST. Activated T cells can remodel tumor vessels to allow more infiltration. To sustain their anti-tumor activities, we have sequentially delivered tumor-activating cytokines (pro-IL2) guided by anti-PD-1 antibody (anti-PD-1-pro-IL2) or radiation-activating TLR agonists to help DC-T cell interaction inside TME to sustain T-cell effector function. Together, we have sequential strategies converting cold to hot tumors and then simultaneously reinvigorates TIL to overcome the limitations of current immunotherapies. Citation Format: Yang-Xin Fu, . The Immune strategies to convert cold to hot tumors and overcome resistances [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4245.

Abstract Cytokines are powerful modulators of antitumor immunity, but their clinical use is constrained by structural instability and systemic toxicity. Although antibody-based cytokine mimetics have recently emerged to activate immune cells in vitro, their therapeutic activity in vivo remains uncertain. Here, using interleukin-15 (IL-15) as a model, we engineered bispecific antibody-based IL-15 mimetics guided by AlphaFold3-assisted structural modeling. Comparative screening of multiple formats identified tandem IL-15 mimetics with strong in vitro bioactivity, but unexpectedly showed minimal antitumor activity in vivo. Strikingly, incorporating TIGIT-directed targeting transformed these mimetics into potent and nontoxic cytokine agonists, resulting in strong tumor control associated with enhanced effector activation and expansion of intratumoral CD8+ stem-like T cells. These findings indicate that current cytokine mimetics have limited activity when used alone and require precise T-cell targeting to achieve therapeutic potency. Our study highlights a strategy to use cytokine mimetics to overcome the mismatch between immune checkpoint blockade and low-potency cis-targeted cytokines, offering a path toward safer and more effective cytokine immunotherapy. Citation Format: Xiangming Liu, Nan Li, Yang-Xin Fu, Zaopeng Yang, . αTIGIT-guided IL-15 mimetics enable potent and safe antitumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2625.

Ferroptosis, an emerging form of regulated cell death driven by iron-dependent lipid peroxidation, represents a promising therapeutic target in oncology. Gynecological malignancies—cervical, endometrial, and ovarian cancers—are frequently associated with therapeutic resistance due to defective cell death regulation. This review delineates cancer-specific ferroptosis regulatory networks across these malignancies. In cervical cancer, high-risk HPV oncoproteins (E6/E7) rewire oxidative stress and lipid metabolism, leading to stage-dependent ferroptosis vulnerability and supporting combination approaches with immunotherapy. In endometrial cancer, ELK1-mediated GPX4 upregulation drives chemoresistance, highlighting ferroptosis induction as a strategy to overcome treatment failure. In ovarian cancer, iron overload promotes metastasis, while p53, lipid-modifying enzymes (SCD1/FADS2), and the tumor microenvironment (e.g., CXCL8/CXCR2 axis) modulate ferroptosis sensitivity, providing avenues to target aggressive subtypes such as clear cell carcinoma. We conclude that targeting ferroptosis offers a transformative strategy for gynecological cancers.

Abstract The clinical success of T cell engagers (TCEs) in hematologic malignancies has been difficult to replicate in solid tumors due to limited efficacy and on-target toxicities, partly driven by CD3-directed activation-induced cell death (AICD) and exhaustion of tumor-infiltrating lymphocytes (TILs). To overcome T cell dysfunction in the tumor microenvironment, we found that IL-10 receptor expression is enriched on antigen-specific T cells and that exogenous IL-10 markedly reduces T cell death while preserving overall T cell numbers. Guided by this insight, we engineered a series of IL-10-integrated TCE formats and identified an optimized design in which IL-10 is fused to the N-terminus of the anti-CD3 arm in a cleavable configuration, generating a pro-TCE (IL10-TCE) with favorable biochemical properties and potent antitumor activity without detectable toxicity. The IL10-TCE enhanced effector function and substantially expanded both total and antigen-specific T cells within tumors, resulting in complete regression of established solid tumors and metastatic lesions across multiple syngeneic and xenograft models, including colon cancer, melanoma, and pancreatic cancer. These findings establish IL-10 incorporation as a generalizable strategy to overcome TCE-induced T cell dysfunction, enabling robust tumor eradication and durable immune protection. Citation Format: Xinxin Wang, Yang-Xin Fu, Zaopeng Yang, . A cleavable IL10-TCE counteracts TCE-induced T cell dysfunction and eradicates solid tumors without toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2626.

Dedifferentiated endometrial carcinoma occurs when a prognostically favorable low-grade endometrial carcinoma transforms into a highly aggressive undifferentiated carcinoma following genomic inactivation of core SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein(s). This typically occurs in a microsatellite-instable molecular context. This study aims to identify the immune evasion mechanisms associated with dedifferentiation. Whole-slide immunohistochemistry-based image analysis was used to compare spatial cancer immunophenotypes and human leukocyte antigen class I (HLA-I) expression between the differentiated and undifferentiated components of 14 SWI/SNF-inactivated dedifferentiated endometrial carcinomas. Flow cytometry and in vivo xenograft studies were performed to gain functional insights. Dedifferentiation was associated with changes in spatial cancer immunophenotypes, most frequently from an inflamed immunophenotype in the differentiated component to an excluded immunophenotype in the undifferentiated component, with loss of tumor HLA-I expression, decreased intraepithelial CD8+ T-cell, and increased stromal PD-L1+ immune infiltrates. Loss of tumor surface HLA-I expression was also observed in the undifferentiated carcinoma from two patient-derived models of dedifferentiated endometrial carcinomas - DDEC1 and DDEC2. By flow cytometry, IFN-γ treatment restored HLA-I expression in DDEC2 (3.5-fold increase, p < 0.05) but not in DDEC1, which harbored inactivating JAK1 mutations. In the in vivo xenograft model of DDEC2, intratumoral injection of IFN-γ restored HLA-I expression in the undifferentiated tumors. These findings implicate the loss of tumor HLA-I expression as an immune evasion mechanism acquired during dedifferentiation in a subset of dedifferentiated endometrial carcinomas. More importantly, IFN-γ can restore tumor HLA-I expression, providing a rationale for combining it with immune checkpoint inhibitors in the treatment of this clinically aggressive cancer type. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Cytokines are powerful modulators of antitumor immunity, but their clinical use is limited by structural instability, short half-life, poor drug-like properties, and severe systemic toxicity. Antibody-based cytokine mimetics have recently emerged to activate immune cells in vitro, but whether these mimetics can overcome the shortcomings of cytokines and exert therapeutic efficacy in vivo remains unclear. Here, we engineered bispecific antibody-based IL-15 mimetics using immunized Alpaca-derived phage display coupled with AlphaFold3-assisted structural screening and comparative screening of multiple formats to identify tandem IL-15 mimetics with strong in vitro bioactivity. Importantly, tandem IL-15R agonistic bispecifics, which simultaneously engage IL-15Rβ and γc, clearly demonstrated antitumor activity in vivo. To better target tumor-infiltrating lymphocytes (TILs), we incorporated a high-affinity anti-TIGIT antibody to guide tandem IL-15Rβγ agonists. This tri-antibody design, αTIGIT-αIL-15Rβγ, resulted in a striking improvement in antitumor activity without detectable systemic toxicity even at high doses. Mechanistically, αTIGIT-αIL-15Rβγ enhanced CD8⁺ T effector function and expanded the number of intratumoral stem-like T cells. Our study highlights a strategy to use TIL-targeted cytokine mimetics to overcome the limitations of native cytokines and enable dose pairing with immune checkpoint blockade (ICB), offering a path toward safer and more effective cytokine immunotherapy.

Abstract T cell engagers (TCEs) have achieved transformative success in B-cell malignancies but show limited efficacy in solid tumors with severe toxicity. Here, we identify insufficient IL-2 signaling as a key bottleneck for sustaining TCE-induced T-cell function. Although exogenous IL-2 enhances TCE efficacy, its systemic administration causes more severe toxicity. To overcome this limitation, we engineered a protease-activatable dual-variable-domain (DVD) as Pro-TCE to reduce its off-tumor toxicity. Furthermore, we designed a mutant IL-2 (3E) with markedly reduced receptor affinity that is inactive in periphery. The construct (DVD-3E) remains inert in circulation and becomes locally activated only upon tumor-specific protease cleavage, coupling T-cell engagement with cis IL-2 signaling. This logic-gated design restricts both TCE and cytokine activity to the tumor microenvironment (TME), enabling potent antitumor responses without systemic toxicity. Mechanistically, DVD-3E enhances the persistence and effector function of preexisting intratumoral T cells, expands TCF1+ progenitor and antigen-specific T cells populations, mitigates exhaustion, and establishes durable immune memory. Notably, DVD-3E treatment increased the frequency of antigen-specific T cells in draining lymph nodes, which were capable of controlling distant tumors and mediating effective tumor regression upon adoptive transfer. These findings define a new design principle for logic gated TCEs that achieve a favorable balance between safety and efficacy, offering a strategy to overcome current therapeutic resistant. Citation Format: Yang-Xin Fu, . Logic-gated T cell engager linked with mutant IL-2 for safer and better effective solid tumor immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7460.

Pancreatic ductal adenocarcinoma (PDAC) presents a substantial challenge due to its resistance to cancer treatments. This limited efficacy is, in part, attributed to the immunosuppressive tumor microenvironment (TME), which impairs effector T (Teff) cell activity. Interleukin-2 (IL-2) is a key cytokine for T cell activation, but its therapeutic use is limited by a short half-life, systemic toxicity, and regulatory T (Treg) activation. To address this limitation, we engineered Bifidobacterium longum, a probiotic obligate anaerobe that selectively colonizes the TME, to continuously secrete Super-mutant IL-2 (SumIL-2), an engineered IL-2 variant that preferentially activates Teff cells over Treg cells, thereby delivering SumIL-2 selectively to the tumor (BifidoSumIL-2). Systemic administration of BifidoSumIL-2 significantly suppressed tumor growth in both subcutaneous tumors and orthotopic PDAC in mice, inducing an improved Teff/Treg ratio. Combining BifidoSumIL-2 with chemotherapy, radiation, and immunotherapy further restrained orthotopic PDAC growth, highlighting its therapeutic potential for difficult-to-treat cancers like PDAC.

The major barrier to clinical translation of αCD137 immunotherapy is separating antitumor efficacy from hepatotoxicity driven by IFN-γ-producing CD8 T cells. We propose a strategy to limit toxicity by promoting contraction of excessively expanded CD8 T cells. We identify CD11c+KLRG1+ effector CD8 T cells (CD11c+TE) as the primary source of IFN-γ, recirculating between blood and secondary lymphoid organs (SLOs), where they undergo apoptosis during contraction. We show that lymphotoxin β receptor (LTβR) signaling restrains this contraction. Mechanistically, lymphotoxin-expressing B cells activate LTβR in fibroblastic reticular cells (FRCs), suppressing apoptosis of CD11c+TE cells in the spleen and sustaining their systemic circulation and liver infiltration. Pharmacological LTβR blockade abrogates hepatotoxicity by reducing the accumulation of IFN-γ-producing CD11c+TE cells while preserving tumor-specific CD8 T cell responses. These findings identify LTβR as a key regulator of effector CD8 T cell persistence and support the use of LTβR antagonists to improve the safety of αCD137-based immunotherapy.

Adoptive T-cell therapies engineered with T-cell receptors (TCRs) or TCR-like antibodies have shown considerable promise in cancer immunotherapy. However, identifying tumor antigen-specific TCR-like antibodies, particularly against human leukocyte antigen-presented neoantigens, remains challenging. Here, we present a function-based, rather than affinity-based, antibody screening platform utilizing Synthetic T-cell receptor and Antigen Receptor (STAR)-T cell libraries. We found that antigen engagement in STAR-T cells triggers synchronous receptor endocytosis and T-cell activation, and we integrated these paired processes into an Endocytosis-Activation (E-A) functional readout for antibody screening. Applying E-A functional screening, we rapidly identified multiple nanobodies targeting the cell-surface antigen CD22 as well as the intracellular neoantigen P53R175H. STAR-T cells engineered with these nanobodies mediated potent anti-tumor efficacy both in vitro and in vivo. Furthermore, this platform yielded nanobodies that can be directly reformatted into other therapeutic modalities, including chimeric antigen receptors and bispecific antibodies, while maintaining cytotoxic function. Overall, the E-A screening platform links antibody discovery directly to T-cell function, providing a robust approach for identifying therapeutic antibodies, especially neoantigen-specific nanobodies, for T cell-based cancer immunotherapy.

Clinical trials related to IL-2- and IL-15 based chimeric cytokines

BACKGROUND:Although PD-1/PD-L1 inhibitors are central to the management of advanced bladder cancer, most patients fail to achieve a meaningful response. While evidence ties MMT to fibrotic disease, its contribution to bladder cancer has yet to be examined. METHODS:We assembled and analysed several complementary data modalities-bulk transcriptomes from TCGA-BLCA (n = 408 tumour, 19 normal) and incorporated single-cell RNA-seq, spatial transcriptomics (nine sections), and two independent immunotherapy cohorts (Kim 2019, n = 348; IMvigor210, n = 298)-to characterize MMT cells and construct an 18-gene MMT signature. Through spatial pseudotime analysis, in vitro overexpression, virtual knockout, FIMO motif scanning, and in vivo tumour models, we identified KLF6 as the key MMT driver. Virtual screening (L1000CDS2) and molecular docking (CB-Dock2) were performed to nominate drugs targeting the KLF6-MMT axis. RESULTS:MMT cells were present in bladder cancer, and the MMT signature was strongly associated with immunotherapy resistance (P = 0.037 for overall survival) and poor prognosis. KLF6 emerged as the key transcriptional driver of MMT, directly binding the ACTA2 proximal promoter. KLF6 overexpression promoted MMT, tumour growth, and PD-L1 upregulation in vivo (P < 0.05 for tumour weight, P < 0.01 for tumour volume), whereas virtual knockout suppressed core MMT effector genes. Spatial analysis revealed enhanced CD274 (PD-L1) expression by MMT cells, which may contribute to immune evasion through engagement of PDCD1 (PD-1) on tumour-infiltrating T cells (P < 0.001). Among the candidates identified by virtual screening, the cardiac glycoside Periplocymarin ranked first (overlap score = 0.375). Docking placed it in the KLF6 C3 pocket-the DNA-binding cleft-with an affinity of -6.5 kcal/mol, a pose consistent with competitive inhibition. CONCLUSIONS:This study provides the first multi-omics characterization of MMT in bladder cancer, identifies KLF6 as a previously unrecognized driver of this transition, and demonstrates that KLF6-driven MMT upregulates tumour PD-L1 through intercellular crosstalk. Furthermore, virtual screening and molecular docking identify Periplocymarin as a candidate compound targeting the KLF6-MMT axis. Our work thus connects KLF6-driven MMT to PD-L1-mediated immune evasion and suggests that disrupting this programme with Periplocymarin may provide a strategy to overcome immunotherapy resistance.

Background KAT6B/A::KANSL1 uterine sarcoma has been recently recognized as a distinct type of uterine sarcoma displaying mixed endometrial stromal and smooth muscle features. Case presentation This report includes two cases of KAT6B::KANSL1 uterine sarcoma with the first case presenting as a prolapsing uterine mass through the cervix. Histologic and molecular analysis performed on the biopsy confirmed the diagnosis of a KAT6B/A::KANSL1 uterine sarcoma. The second is a KAT6B::KANSL1 uterine sarcoma with multiple abdominal recurrences following uterine morcellation at hysterectomy for a presumed benign leiomyoma. Primary cell line models harboring KAT6B::KANSL1 were successfully derived from both cases using fresh tumor tissue, with the aim to determine on whether their growth is estrogen-independent given their consistent strong estrogen receptor (ER) expression. However, in contrast to the respective parental tumors that were strongly ER-positive, the primary cell lines lacked ER expression; hence these cell line models cannot be used to evaluate the effects of estradiol on tumor growth. Conclusion Morcellation may increase the risk of recurrence for KAT6B::KANSL1 uterine sarcoma. While it is feasible to establish primary cell lines from KAT6B::KANSL1 uterine sarcoma, the in vitro cell line models do not retain ER expression.