Immunomodulatory effects of tumor Lactate Dehydrogenase C (LDHC) in breast cancer DOI Creative Commons
Adviti Naik,

Remy Thomas,

Abdulwahab Al-Khalifa

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Background: Immunotherapy has significantly improved outcomes for cancer patients; however, its clinical benefits vary among patients and effectiveness across breast subtypes remains uncertain. To enhance efficacy, it is important to gain more insight into tumor-intrinsic immunomodulatory factors that could be used as therapeutic targets. We previously identified Lactate Dehydrogenase C (LDHC) a promising anti-cancer target due role in regulating cell genomic integrity. In this study, we investigated the effects of tumor LDHC expression on immune responses. Methods: TIMER AND TIDE deconvolution methods were investigate relationship between expression, infiltration T dysfunction. Multiplex cytokine assays flow cytometry analyses monocultures, direct indirect cell-immune co-culture models performed assess effect knockdown secretion inflammatory mediators checkpoint molecules. activity was determined by IFN-γ ELISPot 7-AAD viability cells co-culture. Results: revealed associated with dysfunction worse post-immunotherapy survival melanoma. Depletion three lines (MDA-MB-468, BT-549, HCC-1954) enhanced activation cytolytic function (4-hour co-culture). Analysis monocultures an increase secreted pro-inflammatory cytokines (IFN-γ, GM-CSF, MCP-1, CXCL1), decrease immunosuppressive (IL-6, Gal-9) reduction surface PD-L1 following knockdown. Using 72-hour co-cultures LDHC-silenced cells, observed tumor-promoting (IL-1β, IL-4 IL-6) tumor-inhibiting CXCL1. Furthermore, reduced number CD8+ expressing PD-1 CTLA-4, well TIGIT, TIM3, VISTA. Conclusions: Our findings suggest targeting may improve anti-tumor responses modulating pro- anti-tumorigenic impairing signaling. Further studies are needed elucidate molecular mechanisms which modulates these cancer.

Язык: Английский

Immunomodulatory effects of tumor Lactate Dehydrogenase C (LDHC) in breast cancer DOI Creative Commons
Adviti Naik,

Remy Thomas,

Abdulwahab Al-Khalifa

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Март 19, 2025

Abstract Background Immunotherapy has significantly improved outcomes for cancer patients; however, its clinical benefits vary among patients and efficacy across breast subtypes remains unclear. To enhance immunotherapy efficacy, it is important to gain more insight into tumor-intrinsic immunomodulatory factors that could serve as therapeutic targets. We previously identified Lactate Dehydrogenase C (LDHC) a promising anti-cancer target due role in regulating cell genomic integrity. In this study, we investigated the effects of tumor LDHC expression on immune responses. Methods TIMER AND TIDE deconvolution methods were used investigate relationship between expression, infiltration T dysfunction. Multiplex cytokine assays flow cytometry assess effect knockdown secretion inflammatory molecules checkpoint cells cell-immune co-cultures. activity was determined by IFN-γ ELISPot 7-AAD cytometry. Results analyses revealed associated with dysfunction poorer post-immunotherapy survival melanoma. Silencing lines (MDA-MB-468, BT-549, HCC-1954) enhanced early activation cytolytic activity. better understanding underlying mechanisms, comparative analysis monocultures co-cultures conducted. Following knockdown, observed an increase tumor-derived pro-inflammatory cytokines (IFN-γ, GM-CSF, MCP-1, CXCL1), decrease soluble levels immunosuppressive (IL-6, Gal-9) reduced surface PD-L1 expression. direct co-cultures, pro-tumorigenic (IL-1β, IL-4 IL-6) increased chemokine CXCL1. addition, number CD8 + expressing PD-1 CTLA-4 CTLA-4, TIGIT, TIM3, VISTA reduced. Conclusions Our findings suggest targeting anti-tumor responses modulating addition impairing signaling. Further studies are required elucidate molecular mechanisms which modulates cancer.

Язык: Английский

Процитировано

0
Adult B-Cell Acute Lymphoblastic Leukaemia Antigens and Enriched Pathways Identify New Targets for Therapy DOI Creative Commons

Eithar Mohamed,

Sara Goodman,

Leah Cooksey

и другие.

Onco, Год журнала: 2025, Номер 5(2), С. 19 - 19

Опубликована: Апрель 22, 2025

Background: Adult B-cell acute lymphoblastic leukaemia (aB-ALL) is characterised by abnormal differentiation and proliferation of lymphoid progenitors. Despite a significant improvement in relapse-free overall survival for children with B-ALL, aB-ALL has particularly poor prognosis 5-year rate 20%. First remission achieved most patients, but relapse common high associated mortality. New treatments such as immunotherapy offer an opportunity to extend prevent relapse. Methods: antigens were identified using different sources—immunoscreening, protoarrays, two microarrays one cancer-testis antigen database, review the genomic analyses aB-ALL. A total 385 aB-ALL-associated gene products examined their association patient survival. Results: We 87 transcripts differential expression between healthy volunteers (peripheral blood, bone marrow purified CD19+ cells), 42 that Enrichr analysis showed Transforming Growth Factor-β (TGFβ), Wnt Hippo pathways highly represented (p < 0.02). found SOX4 ROCK1 upregulated all types B-ALL (ROCK1 having p 0.001 except t(8;14) patients), well SMAD3 TEAD4 upregulation being = 0.0008, 0.05 0.001, respectively). Expression each was verified qPCR, only transcript compared volunteer cells 0.01). Conclusions: have number play key roles may act useful targets future strategies.

Язык: Английский

Процитировано

0
Computational Analysis and NGS for Human LDHC Complexed with NAD+ and Ethylamino Acetic Acid (Lung Cancer) DOI Open Access

Uma Kumari,

Saran Sri Nivas,

Mohini Singh

и другие.

International Journal for Research in Applied Science and Engineering Technology, Год журнала: 2024, Номер 12(4), С. 3058 - 3069

Опубликована: Апрель 22, 2024

Abstract: This study presents a multidimensional exploration of the structural and functional characteristics human Lactate Dehydrogenase C (LDHC) complexed with NAD+ ethylamino acetic acid (EAA), focusing on its implications in lung cancer. Leveraging data from Protein Data Bank (PDB) Molecular Modeling Database (MMDB), comprehensive analysis was conducted using various computational tools resources. Structural insights were gained through PDBsum RasMol, elucidating molecular interactions identifying potential drug-target sites. Sequence via BLAST Multiple Alignment provided further understanding conserved sequences motifs. Visualization manipulation structures facilitated by PyMOL, enabling identification active Proteinligand docking studies CB-Dock2 server assessed efficiency LDHC complexation NAD+. validation SAVES ensured reliability complex structure. Additionally, biological network STRING database revealed associations gene ontology classification protein, offering into targeted interventions ancestry protein. approach provides valuable LDHC's role cancer biology offers promising avenues for therapeutic development

Язык: Английский

Процитировано

0
Immunomodulatory effects of tumor Lactate Dehydrogenase C (LDHC) in breast cancer DOI Creative Commons
Adviti Naik,

Remy Thomas,

Abdulwahab Al-Khalifa

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Background: Immunotherapy has significantly improved outcomes for cancer patients; however, its clinical benefits vary among patients and effectiveness across breast subtypes remains uncertain. To enhance efficacy, it is important to gain more insight into tumor-intrinsic immunomodulatory factors that could be used as therapeutic targets. We previously identified Lactate Dehydrogenase C (LDHC) a promising anti-cancer target due role in regulating cell genomic integrity. In this study, we investigated the effects of tumor LDHC expression on immune responses. Methods: TIMER AND TIDE deconvolution methods were investigate relationship between expression, infiltration T dysfunction. Multiplex cytokine assays flow cytometry analyses monocultures, direct indirect cell-immune co-culture models performed assess effect knockdown secretion inflammatory mediators checkpoint molecules. activity was determined by IFN-γ ELISPot 7-AAD viability cells co-culture. Results: revealed associated with dysfunction worse post-immunotherapy survival melanoma. Depletion three lines (MDA-MB-468, BT-549, HCC-1954) enhanced activation cytolytic function (4-hour co-culture). Analysis monocultures an increase secreted pro-inflammatory cytokines (IFN-γ, GM-CSF, MCP-1, CXCL1), decrease immunosuppressive (IL-6, Gal-9) reduction surface PD-L1 following knockdown. Using 72-hour co-cultures LDHC-silenced cells, observed tumor-promoting (IL-1β, IL-4 IL-6) tumor-inhibiting CXCL1. Furthermore, reduced number CD8+ expressing PD-1 CTLA-4, well TIGIT, TIM3, VISTA. Conclusions: Our findings suggest targeting may improve anti-tumor responses modulating pro- anti-tumorigenic impairing signaling. Further studies are needed elucidate molecular mechanisms which modulates these cancer.

Язык: Английский

Процитировано

0