Necroptosis stimulates interferon-mediated protective anti-tumor immunity

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 10, 2024

Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed immunization with necroptotic cells conferred protection against subsequent tumor challenge. Since RIPK3 can also promote apoptosis and NF-κB-dependent inflammation, it remains difficult to determine contribution necroptosis-associated release damage-associated molecular patterns (DAMPs) in anti-tumor immunity. Here, we describe a system allows us selectively induce RIPK3-dependent necroptosis or minimal cytokine expression. In syngeneic challenge model, superior Surprisingly, this protective effect required CD4+ T rather than CD8+ dependent host type I interferon signaling. Our results provide evidence death-dependent production following sufficient elicit

Language: Английский

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Spatial distribution of tertiary lymphoid structures in the molecular and clinical context of non-small cell lung cancer

Cellular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Introduction Tertiary lymphoid structures (TLS) are lymphocyte aggregates resembling secondary organs and pivotal in cancer immunity. The ambiguous morphological definition of TLS makes it challenging to ascertain their clinical impact on patient survival response immunotherapy. Objectives This study aimed characterize hematoxylin-eosin tissue sections from lung patients, assessing occurrence relation the local immune environment, mutational background, outcome. Methods Two pathologists evaluated one whole section resection specimens 680 NSCLC patients. were spatially quantified within tumor area or periphery further categorized based presence germinal centers (mature TLS). Metrics integrated with cell counts, genomic transcriptomic data, correlated parameters. Results present 86% 536 evaluable cases, predominantly periphery, a median eight per case. Mature found 24% cases. positively increased plasma (CD138+) lymphocytic (CD3+, CD8+, FOXP3+) infiltration. Tumors higher burden exhibited numbers peripheral TLS. overall quantity was independently associated improved survival, irrespective maturation status. prognostic association held true for but not Conclusion is common correlation specific phenotype suggests biological relevance reaction. significance this scoring system routine has potential augment diagnostic algorithms

Language: Английский

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TMEM115 as an Oncogenic and Immunological Biomarker in Hepatocellular Carcinoma

Liver International, Journal Year: 2025, Volume and Issue: 45(4)

Published: March 7, 2025

Transmembrane (TMEM) proteins are involved in fundamental biological processes such as material transport and signal transduction. TMEM115 is a member of the TMEM protein family, but its significance hepatocellular carcinoma (HCC) remains unclear. In this study, we investigate clinical predictive potential functions HCC. Bioinformatics was used to mRNA expression immune infiltration score. Through multiplex immunohistochemistry analysis, assessed association with HCC patient features, prognosis cell vitro vivo experiments, evaluated cells impact on microenvironment. levels were significantly higher tissues compared paracancerous liver tissues. Its correlated characteristics overall survival patients. tissues, corresponded lower proportions CD66b+ neutrophils CD8+ T proportion CD4+ cells. Furthermore, patients low displayed programmed death ligand-1 lymphocyte activation gene 3 expression. Functionally, knockdown inhibited proliferation, migration invasion orthotopic models, growth affected Our findings show promising prognostic indicator for hold promise predicting responses therapy, emphasising relevance intricate involvement microenvironment

Language: Английский

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Targeting DKK3 to remodel tumor immune microenvironment and enhance cancer immunotherapy

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 9, 2025

Language: Английский

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A frameshift-generated cancer neoepitope that controls tumor burden in prophylaxis as well as therapy

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Insertion or deletion of one two base pairs within a coding region causes frameshift, which has the potential to generate neoepitopes (InDel-generated neoepitopes) that lack self-counterpart and are entirely novel. Despite obvious appeal InDel-generated neoepitopes, demonstration such candidate can elicit CD8 T-cell response, no actually control tumors in vivo have been reported thus far. Here, mouse colon carcinoma line, we identify 11 InDels, only generates neoepitope elicits tumor models prophylaxis as well therapy. Although this self-counterpart, it low affinity (IC50 33,937.60 nM) for its MHC I allele. I, antitumor activity through T cells. Furthermore, cells elicited by neoepitope, like created point mutations, show notably less exhaustion than classical immunogenic epitopes. Ironically, follows same rules noted most control–mediating generated mutations poor alleles.

Language: Английский

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Potential Mechanisms for Immunotherapy Resistance in Adult Soft-Tissue Sarcoma

Targeted Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

Soft-tissue sarcomas represent a diverse group of rare malignancies originating from mesenchymal tissue, accounting for less than 1% adult cancers in the USA. With over 13,000 new cases and around 5350 deaths annually, patients with metastatic soft-tissue face limited therapeutic options an estimated median overall survival 18 months. While immunotherapy has demonstrated effectiveness several cancers, its application remains challenging owing to tumors' largely "cold" immunological environment, characterized by low levels tumor-infiltrating lymphocytes lack sarcoma-specific biomarkers. This review examines potential mechanisms underlying resistance sarcomas, including complex interplay between innate adaptive immunity, tumor microenvironment, role immune-related genes. Despite preliminary findings suggesting correlations immune profiles histological subtypes, consistent biomarkers predicting immunotherapeutic responses across sarcoma types are absent. Emerging strategies focus on converting tumors "hot" tumors, enhancing their susceptibility immunologic activation. research is ongoing, personalized treatment approaches may offer hope overcoming inherent heterogeneity seen ultimately aiming improve outcomes affected patients.

Language: Английский

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GIMAP8 could serve as a potential prognostic factor for lung adenocarcinoma and is closely related to immunity

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 2, 2025

GTPase IMAP family member 8 (GIMAP8) plays a key role in pathophysiology of several malignancies. The objective this current research endeavor was to investigate the prognosis value GIMAP8 lung adenocarcinoma and examine how it relates immunity. Expression profiles associated with related clinical details were acquired from Cancer Genome Atlas database, we conducted survival analysis, enrichment analysis immune infiltration studies. Additionally, evaluated effect on radiation resistance tumor by vivo vitro experiments. Our results showed that tissues exhibited lower levels compared nearby normal tissues. Furthermore, decreased expression strongly correlated poorer OS. is closely formation cells. GSEA identified multiple signaling pathways linked GIMAP8, including immune-related, chemokine, cell adhesion molecule, NF-κB pathways. checkpoint molecules, mutational burden, neoantigen cells, microenvironment. found have an inhibitory response. Moreover, may also influence tumors.

Language: Английский

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Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy

Published: Jan. 1, 2024

The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether ICT enhance immunity distinct or overlapping mechanisms remains unclear. Here, we compared effective tumor-specific mutant neoantigen (NeoAg) anti-CTLA-4 anti-PD-1 in preclinical models. Both NeoAg induce expansion intratumoral NeoAg-specific CD8 cells, though the degree acquisition effector activity was much more substantial following vaccination. Further, found that are particularly adept at inducing proliferating stem-like cells. Single cell receptor (TCR) sequencing revealed TCR clonotype diversity relates their phenotype functional state associated specific immunotherapies employed. Effective required both CD4 While affected compartment, it less an extent than observed anti-CTLA-4, which notably induced ICOS+Bhlhe40+ Th1-like and, when combined anti-PD-1, a small subset Th2-like Although expanded M1-like iNOS+ macrophages, rather suppressed (as ICT) M2-like CX3CR1+CD206+ vaccine adjuvant. combining vaccination superior efficacy either isolation, highlighting utility these modalities cancer.

Language: Английский

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Neoantigen-specific T-cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer

Deleted Journal, Journal Year: 2024, Volume and Issue: 32(3), P. 200835 - 200835

Published: June 15, 2024

CD4

Language: Английский

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Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114875 - 114875

Published: Oct. 23, 2024

Language: Английский

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