Early-Stage Luminal B-Like Breast Cancer Exhibits a More Immunosuppressive Tumor Microenvironment than Luminal A-Like Breast Cancer

Biomolecules, Год журнала: 2025, Номер 15(1), С. 78 - 78

Опубликована: Янв. 7, 2025

Breast cancer is a heterogeneous malignant disease with varying prognosis and classified into four molecular subtypes. It remains one of the most prevalent cancers globally, tumor microenvironment playing critical role in progression patient outcomes. This study evaluated samples from 40 female patients luminal A B breast cancer, utilizing flow cytometry to phenotypically characterize immune cells present within tissue. The B-like exhibited increased infiltration CD4+ cells, regulatory T (Tregs), Th17 decreased levels NK γδ Th1 follicular which indicative more immunosuppressive microenvironment. These findings suggest that tumors have less supportive effective anti-tumor responses compared tumors. enhances understanding immunological differences between subtypes identifies potential new therapeutic targets biomarkers could drive advancements precision medicine for management.

Язык: Английский

---

GPR55 in the tumor microenvironment of pancreatic cancer controls tumorigenesis

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 16, 2025

The G protein-coupled receptor 55 (GPR55) is part of an expanded endocannabinoid system (ECS), and plays a pro-tumorigenic role in different cancer models, including pancreatic cancer. Next to cells, various cells the immune tumor microenvironment (TME) express receptors ECS that critically determine growth. GPR55 has been widely described, but its TME not well understood. We intended uncover immunity model ductal adenocarcinoma (PDAC). To this end, KPCY cell line or GPR55-overexpressing (KPCY55) from murine PDAC were subcutaneously injected into wildtype (WT) knockout (KO) mice, populations evaluated by flow cytometry. Deficiency led reduced weight volume, altered composition tumors, favoring anti-tumorigenic environment increasing number CD3+ T particularly CD8+ expression PDL1 on macrophages. RNA-seq pathway analysis revealed higher activity KPCY55 tumors KO vs. WT mice. In addition, mice displayed increased levels chemokines Cxcl9 Cxcl10. Migration towards CXCL9 was comparison suggesting CXCR3/CXCL9 axis involved influx Notably, anti-PD-1 immunotherapy burden while effect absent Our study indicates may drive growth suppressing functions, such as migration, PDAC, making it interesting target for immunotherapies.

Язык: Английский

---

CD4 T cell depletion increases memory differentiation of endogenous and CAR T cells and enhances the efficacy of Super2 and IL-33-armored CAR T cells against solid tumors

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(2), С. e009994 - e009994

Опубликована: Фев. 1, 2025

Background Responsiveness to chimeric antigen receptor (CAR) T cell therapy correlates with CAR expansion and persistence in vivo. Multiple strategies improve by increasing stem-like properties or sustaining activity combination therapies. Here, we describe the intrinsic ability of cells differentiate into memory cells, effect cytokine armoring, neoadjuvant CD4 depletion on tumor-specific endogenous cells. Methods TRP1-specific NKG2D alone Super2+IL-33 (S233) armoring and/or were evaluated immunocompetent B16F10 melanoma MC38 colon carcinoma models without preconditioning. We characterized precursors, establishment circulating (T CIRC ) resident RM subsets, protect against secondary tumors. Results had no primary tumor growth mice unless they combined S233 depletion. Unarmored expressed a phenotype tumor-draining lymph node differentiated lymphoid organs skin. In contrast, S233-armored exhibited an activated effector inefficiently central Combining unarmored increased Either induced activation that both synergized increase Conclusions TRP-1-specific have subsets but are non-protective improved responses limited generation. potentiated generation resulted protection rechallenge.

Язык: Английский

---

Sex and Age-Based Differences in Immune Responses to a Peptide Vaccine for Melanoma in Two Clinical Trials

Vaccines, Год журнала: 2025, Номер 13(2), С. 194 - 194

Опубликована: Фев. 16, 2025

Little is known about the impact of patient age and biological sex on immune responses to melanoma vaccines, especially CD4+ T cell peptides presented by Class II MHC molecules. We assessed antibody a mixture six helper (6MHP) CD8+ when vaccinating with 12 class I MHC-restricted (12MP) plus either 6MHP or tetanus peptide (Tet). hypothesized that would be greater in men younger patients. found differences response sex, but they favored female patients were only evident for Tet weak trend higher 12MP vaccinated + Tet. The age-based inoculated These findings reinforce importance assessing sex- cancer vaccines other therapies. There also need understand reasons such differences.

Язык: Английский

---

Vaccines in Melanoma

Surgical Oncology Clinics of North America, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

---

Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine

iScience, Год журнала: 2025, Номер 28(4), С. 112120 - 112120

Опубликована: Март 15, 2025

Alisertib is a potent aurora A kinase inhibitor in clinical trials for cancer treatment, but its efficacy on vaccines remains unclear. Here, we developed DNA vaccine targeting glypican-3 (pGPC3) and evaluated with alisertib hepatocellular carcinoma (HCC) models. The combination therapy of pGPC3 significantly inhibited subcutaneous tumor growth, enhanced the induction maturation CD11c+ CD8+CD11c+ dendritic cells (DCs), expanded tumor-specific CD8+ T cell responses. depletion abolished anti-tumor effects, underscoring essential role functional Moreover, combined treatment promoted memory induction, providing long-term protection. In liver orthotopic models, demonstrated therapeutic through These results indicate that enhances vaccine's effect, offering promising strategy HCC treatment.

Язык: Английский

---

A pan-cancer analysis reveals the oncogenic and immunological role of insulin-like growth factor 2 mRNA-binding protein family members

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Март 15, 2025

Abstract Purpose To investigate the expression and clinical significance of insulin-like growth factor 2 mRNA-binding protein family members (IGF2BPs) in pan-cancer evaluate their potential as targets for tumor immunotherapy. Methods Based on data from cancer genome atlas (TCGA) database, analysis was conducted to examine IGF2BPs twenty-two tumors. Results Differential showed high most tissues. Survival mutation analyses suggested that overexpression associated with poor prognosis status certain Methylation revealed methylation levels IGF2BP1/2/3 tumors were intricately linked mRNA expression, patient prognosis, immune cell infiltration. Enrichment indicated abnormal various common tumor-related pathways different tumors, including AMPK, Hippo, PI3K-Akt, EMT, p53. In addition, correlation closely related immunotherapy-related indicators (immune infiltration, major histocompatibility complex (MHC), checkpoints, burden (TMB), microsatellite instability (MSI)) some Drug sensitivity sensitive chemotherapeutic drugs (alvocidib, dasatinib, trametinib, selumetinib). Conclusion exhibit significantly are pathological stage, mutational status, levels, relevant immunotherapy multiple Moreover, may play an oncogenic role by activating signaling pathways. Therefore, be prognostic markers therapy drug therapy.

Язык: Английский

---

New insights into T cell metabolism in liver cancer: from mechanism to therapy

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Март 23, 2025

Abstract Liver cancer is the sixth most common worldwide and third cause of mortality. The development progression liver metastases a multifaceted process involving numerous metabolic pathways. T cells have protective role in defense against cancer, manipulating pathways can alter their antitumor activity. Furthermore, cell nutrition competition lead to dysfunction through various molecular mechanisms. Some nanomaterials drugs improve metabolism promote anti-liver function cells. This review discusses current literature regarding changes targeted therapy for cancer. promise challenges studying target treating are also addressed. Targeting promising approach

Язык: Английский

---

Transcriptomic signatures in peripheral CD4+T-lymphocytes may reflect melanoma staging and immunotherapy responsiveness prior to ICI initiation

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 28, 2025

Promoting adaptive immunity with ICIs has drastically improved melanoma prognosis, but not for all patients. Some cases relapse in the first few months, while others keep durable benefit, even after immunotherapy discontinuation. To identify cellular/molecular signatures peripheral blood that could differentiate advanced from metastatic and predict dynamics primary/secondary immune escape, we examined 100 consecutive patients stage III/IV scheduled to start ICIs. At diagnosis, a multiparameter flow cytometric analysis purification scheme using standard conjugated antibodies were performed individuals prior ICI initiation. In each stage(III/IV) according their RFS/PFS, retrospectively selected clearest clinical outcomes focused our on extreme responders(n=7) non-responders(n=7) characterize transcriptomes of circulating CD4+T-cells by bulk RNA-seq, Differential Expression Analysis(DEA)and Gene Ontology(GO)enrichment analysis. Based patient cohort, differentially expressed genes(DEGs)and key-pathways appear preferentially activated III vs. IV melanoma, long short responders. Although immune-cells did numerically differ both sets analysis(staging responsiveness), DEA GO data showed be clustered separately, identifying 189vs.92 DEGs IV/III 101vs.47 early progressors/long These functionally implicated distinct pathways. For cases: inflammatory response(logp-value=-9.2:ADGRE5/2,CYBA,GRN,HMOX1,IRF5,ITGAM), immunity(logp-value=-7.7:CD1C,CD74,CYBB,NCF2,CTSA,S100A8/9,BCL3,FCER1G), T-cell activation(logp-value=-6.3:BCL3,CD1C,CD74,FCER1G,FGL2)and lipid metabolism/catabolism(logp-value=-2.5/-2.6:ARF3,GPX1,MVD,OCRL,PCCB,CTSA,PNPLA2,NAGLU,GBA2,ABHD4); early-progressors ICIs: effector processing(logp-value=-13.7:BCL6,FGR,HLA-DQA1/DQB1,HLA-DRA,HLA-DRB1/DRB5,NKG7,SLC11A1,TYROBP,SPON2,HAVCR2),PD-1(logp-value=-10.2:HLA-DQA1/DQB1,HLA-DRA,HLA-DRB1/DRB5)and IFN signaling(logp-value=-8.5: HLA-DQA1/DQB1,HLA-DRA,HLA-DRB1/DRB5,NCAM1,IFITM3),positive regulation activation(logp-value=-7.7:BCL6,HLA-DQA1/DQB1,HLA-DRA,HLA-DRB1/DRB5,SASH3,HAVCR2)and CD28 co-stimulation(logp-value=-10.3:HLA-DQA1/DQB1,HLA-DRA,HLA-DRB1/DRB5), supporting an immune-mediated behavior. Specific pathways marker genes may predetermine staging resistance.

Язык: Английский

---

Acetylation and deacetylation dynamics in stress response to cancer and infections

Seminars in Immunology, Год журнала: 2025, Номер 78, С. 101957 - 101957

Опубликована: Апрель 26, 2025

Язык: Английский

---