Targeting Liver Metastases to Potentiate Immunotherapy in MS-Stable Colorectal Cancer—A Review of the Literature DOI Open Access
Oran Zlotnik,

Lucyna Krzywoń,

Jessica Bloom

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(21), P. 5210 - 5210

Published: Oct. 30, 2023

Immunotherapy has revolutionized the treatment of several cancers, including melanoma and lung cancer. However, for colorectal cancer, it is ineffective 95% patients with microsatellite-stable disease. Recent evidence suggests that liver’s immune microenvironment plays a pivotal role in limiting effectiveness immunotherapy. There also to show targeting liver metastases locoregional therapies, such as surgery or irradiation, could potentiate immunotherapy these patients. This review presents from preclinical studies regarding underlying mechanisms clinical support this approach. Furthermore, we outline potential directions future trials. innovative strategy potentially establish an effective MS-stable cancer patients, which are currently considered resistant.

Language: Английский

Serine Depletion Promotes Anti-Tumor Immunity by Activating Mitochondrial DNA-mediated cGAS-STING Signaling DOI
Suchandrima Saha, Monisankar Ghosh, Jinyu Li

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(16), P. 2645 - 2659

Published: June 11, 2024

Abstract Serine is critical for supporting cancer metabolism, and depriving malignant cells of this nonessential amino acid exerts antineoplastic effects, in large part, through disrupting metabolic pathways. Given the intricate relationship between metabolism immune system, defects imposed by serine deprivation might impact tumor-targeting immunity. In study, we demonstrated that restricting endogenous exogenous sources colorectal results mitochondrial dysfunction, leading to DNA (mtDNA) accumulation cytosol consequent cGAS-STING1-driven type I IFN secretion. Depleting mtDNA or blocking its release attenuated cGAS-STING1 activation during deprivation. vivo studies revealed limits tumor growth, accompanied enhanced signaling intratumoral infiltration effector cells. Notably, tumor-suppressive immune-enhancing effects restriction were impaired T-cell depletion receptor blockade. Moreover, limited immunostimulatory Lastly, increased sensitivity tumors an checkpoint inhibitor targeting PD-1. Taken together, these findings reveal a role as suppressor antitumor immunity, suggesting may be employed enhance immunogenicity improve responsiveness inhibitors. Significance: Depriving provokes perturbations induce cytosolic subsequent cGAS-STING signaling, stimulating responses can with PD-1 targeted therapy. See related commentary Borges Garg, p. 2569

Language: Английский

Citations

13
Early-onset cancers: Biological bases and clinical implications DOI Creative Commons
Gianluca Mauri, Giorgio Patelli, Andrea Sartore‐Bianchi

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101737 - 101737

Published: Sept. 1, 2024

Language: Английский

Citations

7
Tryptophan As a New Member of RNA‐Induced Silencing Complexes Prevents Colon Cancer Liver Metastasis DOI Creative Commons
Fangyi Xu, Yi Ren,

Yun Teng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 20, 2024

Abstract Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the miR has never been demonstrated. Here, as proof‐of‐concept, tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p interacts with Ago2. Trp/Ago2/miR‐193a increases via enhancing RNase activity. Other miR‐103 miR‐107 in enhance by targeting same genes. Mechanistically, Trp‐binding pockets PIWI domain Ago2 to mediated This newly formed Ago2/Trp/miR‐193a‐3p more efficient than alone inhibiting expression targeted genes colon cancer liver metastasis. The findings show that through communication RNA‐induced silencing complexes (RISC), which provides basis for based therapy.

Language: Английский

Citations

4
Synthetic GPR84 Agonists in Colorectal Cancer: Effective in THP-1 Cells but Ineffective in BMDMs and MC38 Mouse Tumor Models DOI Open Access
Marlene Schwarzfischer, Marion Walker, Michele Curcio

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 490 - 490

Published: Jan. 9, 2025

Tumor-associated macrophages (TAMs) in the colorectal cancer (CRC) microenvironment promote tumor progression but can be reprogrammed into a pro-inflammatory state with anti-cancer properties. Activation of G protein-coupled receptor 84 (GPR84) is associated macrophage polarization, making it potential target for CRC therapy. This study evaluates effects GPR84 agonists 6-OAU and ZQ-16 on activation efficacy. expression THP-1 murine BMDMs was analyzed using flow cytometry. Macrophages were treated or ZQ-16, cytokine levels, reactive oxygen species (ROS) production, phagocytosis assessed qPCR functional assays. Anti-cancer tested subcutaneous MC38 model, oral intraperitoneal agonist administration. Pharmacokinetics compound stability also evaluated. In macrophages, increased cytokines ROS showing similar effects. However, neither induced responses, macrophages. vivo, both failed to inhibit growth model despite systemic exposure. Current lack efficacy promoting activity, limiting their as therapies.

Language: Английский

Citations

0
Therapeutic role of immune cells against colon cancer DOI
Manoj Kumar Gupta,

Gayatri Gouda,

Ramakrishna Vadde

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 127 - 146

Published: Jan. 1, 2025

Language: Английский

Citations

0
Organoid models: applications and research advances in colorectal cancer DOI Creative Commons

Yijie Wu,

Sha Yu,

Xingpo Guo

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 7, 2025

This review summarizes the applications and research progress of organoid models in colorectal cancer research. First, high incidence mortality rates are introduced, emphasizing importance organoids as a model. Second, this provides detailed introduction to concept, biological properties, organoids, including their strengths mimicking structural functional aspects organs. article further analyzes adult stem cell-derived pluripotent discusses advancements for basic research, drug development, personalized treatment evaluation prediction, regenerative medicine. Finally, prospects applying technology its significant value improving patient survival rates. In conclusion, systematically explains highlighting tremendous potential promising

Language: Английский

Citations

0
Construction of hot tumor classification models in gastrointestinal cancers DOI Creative Commons
Chien-Jung Huang, Guan‐Ting Liu,

Yi-Chen Yeh

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 21, 2025

Gastrointestinal (GI) cancers account for more than one-third of cancer-related mortality, and the prognosis late-stage patients remains poor. Immunotherapy has been proven to extend survival at advanced stages; however, challenges persist in patient selection overcoming drug resistance. Tumor-infiltrating lymphocytes (TILs) tertiary lymphoid structures (TLS) tumor microenvironment (TME) have found be associated with anti-tumor immune responses. 'Hot tumors' high levels infiltration tend respond better checkpoint inhibitor (ICI) therapy, making them potential biomarkers ICI treatment. To explore predicting immunotherapy response GI cancers, we downloaded gene expression profiles seven from The Cancer Genome Atlas (TCGA) database characterized their TME, classifying samples into hot/cold subgroups. Furthermore, developed a computational framework construct cancer-specific hot classification models only few genes. External independent datasets qPCR experiments were used verify performance our few-gene models. We constructed identify tumors two nine results showed that B cells are important determination, identified significantly TLS. They not overexpress TLS marker genes but also presence whole-slide images. Further, two-gene model was effectively distinguish between cold subgroups cholangiocarcinoma, providing an opportunity stratifying clinical settings. In conclusion, established models, which can easily integrated practice, subgroups, may serve as response.

Language: Английский

Citations

0
A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression DOI Creative Commons
Cheng Wang, Minghao Zhang, Shunyao Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(11), P. 4819 - 4831

Published: Sept. 14, 2024

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon patients remains relatively low. This closely related immunosuppressive microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts range of anti-tumor activities in lung cancer. Here, we found upregulation

Language: Английский

Citations

2
Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression DOI Creative Commons
Amanda L. McCormick, Trevor S. Anderson, Elizabeth A. Daugherity

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 2, 2023

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy enhance clinical experience CRC involves use dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for growth progression. In this report, we target pericytes expressing DLK1 clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in syngeneic mouse model cancer. Our pre-clinical data demonstrate αDC1 vaccine's ability induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity ablating tumor vasculature. This work, overall, provides foundation further interrogate immune-mediated mechanisms protection order help devise efficacious αDC1-based strategies patients CRC.

Language: Английский

Citations

4
Irreversible Electroporation has More Synergistic Effect with Anti‐PD‐1 Immunotherapy than Thermal Ablation or Cryoablation, in a Colorectal Cancer Model DOI Creative Commons
Minhan Jiang, Qi Shao, Joseph R. Slaughter

et al.

Advanced Therapeutics, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

Abstract Boosting the response rate of immune checkpoint blockade (ICB) therapy to improve treatment efficacy is a primary goal in cancer immunotherapy. One promising approaches involves focal tumor ablation reduce burden and trigger situ vaccination. Even though this combination strategy has demonstrated enhanced therapeutic outcomes both preclinical research clinical trials, limited comparatively investigated diverse techniques. The optimal choice among techniques remains largely unknown. In murine colorectal model (MC‐38), anti‐PD‐1 with thermal ablation, cryoablation, irreversible electroporation (IRE) evaluated, utilizing well‐characterized miniature probes. model, ICB monotherapy effect controlling growth. IRE exhibits most favorable synergistic immunotherapy than or leading greatest growth delay, longest tumor‐free survival, highest protection against secondary challenge. Furthermore, co‐administration significantly fosters infiltration CD8+ T cells into coupled remarkable stem‐like progenitor phenotype. findings demonstrate that stands as modality can potentiate antitumor when poorly responding monotherapy.

Language: Английский

Citations

1