Targeting of TAMs: can we be more clever than cancer cells?

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(12), P. 1376 - 1409

Published: Nov. 8, 2024

АBSTRACT: With increasing incidence and geography, cancer is one of the leading causes death, reduced quality life disability worldwide. Principal progress in development new anticancer therapies, improving efficiency immunotherapeutic tools, personification conventional therapies needs to consider cancer-specific patient-specific programming innate immunity. Intratumoral TAMs their precursors, resident macrophages monocytes, are principal regulators tumor progression therapy resistance. Our review summarizes accumulated evidence for subpopulations number biomarkers, indicating predictive value clinical parameters carcinogenesis resistance, with a focus on solid cancers non-infectious etiology. We present state-of-the-art knowledge about tumor-supporting functions at all stages highlight recently identified by single-cell spatial analytical methods, that discriminate between tumor-promoting tumor-inhibiting TAMs, where both subtypes express combination prototype M1 M2 genes. focuses novel mechanisms involved crosstalk among epigenetic, signaling, transcriptional metabolic pathways TAMs. Particular attention has been given link cell metabolism epigenetic histone lactylation, which can be responsible unlimited protumoral Finally, we explain how interfere currently used therapeutics summarize most advanced data from trials, divide into four categories: inhibition TAM survival differentiation, monocyte/TAM recruitment tumors, functional reprogramming genetic enhancement macrophages.

Language: Английский

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Advancements in proteogenomics for preclinical targeted cancer therapy research

Biophysics Reports, Journal Year: 2025, Volume and Issue: 11(1), P. 56 - 56

Published: Jan. 1, 2025

Advancements in molecular characterization technologies have accelerated targeted cancer therapy research at unprecedented resolution and dimensionality. Integrating comprehensive multi-omic profiling of a tumor, proteogenomics, marks transformative milestone for preclinical research. In this paper, we initially provided an overview proteogenomics research, spanning genomics, transcriptomics, proteomics. Subsequently, the applications were introduced examined from different perspectives, including but not limited to genetic alterations, quantifications, single-cell patterns, post-translational modification levels, subtype signatures, immune landscape. We also paid attention combined multi-omics data analysis pan-cancer analysis. This paper highlights crucial role elucidating mechanisms tumorigenesis, discovering effective therapeutic targets promising biomarkers, developing subtype-specific therapies.

Language: Английский

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Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(3), P. e010959 - e010959

Published: March 1, 2025

Background Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote a hostile tumor microenvironment and associated worse clinical outcomes PROC. We evaluated the safety preliminary efficacy of PY159, an agonist antibody to Triggering receptor expressed on myeloid cells-1 (TREM1) that reprograms immunosuppressive intratumoral cells, PY314, antagonist cells-2 (TREM2) depletes tumor-associated macrophages, as single agents combination pembrolizumab subjects Methods PY159 PY314 were individually Patients treated monotherapy (PY159 3 mg/kg or 10 mg/kg), based recommended dose for expansion derived from phase 1a studies. At time first progression, could continue study drug crossover therapy (200 mg) every weeks at discretion investigator. Disease assessment by Response Evaluation Criteria Solid Tumor version 1.1 was performed 6 weeks. Results 17 enrolled (median age 67, range 22–77; median prior therapies 6, 2–18) 16 65.5, 49–81; 4, 2–10). 7 8 crossed over therapy. Safety events included following: treatment-related adverse occurred 15 (88.2%) 9 (56.3%) PY314. Infusion-related reactions (35.3%) (18.8%) Immune-related 13 (76.5%) (arthralgias) 1 patient (6.3%) (diarrhea). Serious (36.3%) (1 related) 12 (75%) (all unrelated). The best radiographic response stable disease 8/16 (50%; weeks, 9–33), it 6–36). Median PFS 2.76 months 2.69 respectively. There no responses arm. Conclusions Both well tolerated, acceptable profile, both pembrolizumab. warrant further investigation heavily pretreated

Language: Английский

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Toward clinical applications of spatial-omics in cancer research

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(12), P. 1771 - 1773

Published: Dec. 17, 2024

Language: Английский

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