Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(7), P. 1045 - 1062

Published: June 3, 2024

Language: Английский

---

Novel research and future prospects of artificial intelligence in cancer diagnosis and treatment

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Nov. 27, 2023

Research into the potential benefits of artificial intelligence for comprehending intricate biology cancer has grown as a result widespread use deep learning and machine in healthcare sector availability highly specialized datasets. Here, we review new approaches how they are being used oncology. We describe might be detection, prognosis, administration treatments introduce latest large language models such ChatGPT oncology clinics. highlight applications omics data types, offer perspectives on various types combined to create decision-support tools. also evaluate present constraints challenges applying precision Finally, discuss current may surmounted make useful clinical settings future.

Language: Английский

---

First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 2087 - 2098

Published: Aug. 1, 2023

Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy targeted therapies remains the only therapeutic option for stable (MSS) tumors. The single-arm, phase 1b/2 MEDITREME trial evaluated safety and efficacy of durvalumab plus tremelimumab combined mFOLFOX6 in first line, 57 RAS-mutant unresectable CRC. Safety was primary objective Ib; no issue observed. 2 terms 3-month progression-free survival (PFS) MSS tumors met, PFS 90.7% (95% confidence interval (CI): 79.2-96%). For secondary objectives, response rate 64.5%; median 8.2 months CI: 5.9-8.6); overall not reached We observed higher tumor mutational burden lower genomic instability responders. Integrated transcriptomic analysis underlined that high signature low epithelial-mesenchymal transition were associated better outcome. Immunomonitoring showed induction neoantigen NY-ESO1 TERT blood tumor-specific T cell PFS. combination durvalumab-tremelimumab tolerable promising clinical activity mCRC. Clinicaltrials.gov identifier: NCT03202758 .

Language: Английский

---

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 632 - 645

Published: March 1, 2023

Abstract The historical lack of preclinical models reflecting the genetic heterogeneity multiple myeloma (MM) hampers advance therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse developed bone marrow (BM) tumors fulfilling pathogenesis. Integrative analyses ∼500 ∼1,000 patients revealed a common MAPK–MYC pathway that accelerated time progression from precursor states across heterogeneous MM. MYC-dependent conditioned immune evasion mechanisms remodeled BM microenvironment differently. Rapid MYC-driven progressors exhibited high number activated/exhausted CD8 + cells with reduced immunosuppressive regulatory (T reg ) cells, while late MYC acquisition slow was associated lower cell infiltration more abundant cells. Single-cell transcriptomics functional assays defined ratio versus as predictor response checkpoint blockade (ICB). In clinical series, T/T ratios underlie early untreated smoldering MM, correlated relapse newly diagnosed under Len/Dex therapy. ICB-refractory models, increasing cytotoxicity or depleting reversed immunotherapy resistance yielded prolonged control. Our experimental enable correlation immunological traits therapy responses, which may inform next-generation trials.

Language: Английский

---

Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 225 - 237.e5

Published: Jan. 25, 2024

Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given known epigenetic regulation critical SCLC programs, we hypothesized that subtype-specific patterns DNA methylation could be detected tumor or blood from patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) two cohorts totaling 179 patients and using machine learning approaches, report a highly accurate methylation-based classifier (SCLC-DMC) can distinguish subtypes. We further adjust for circulating-free (cfDNA) subtype plasma. cfDNA (cfDMC), demonstrate phenotypes evolve during disease progression, highlighting need longitudinal tracking clinical treatment. These data establish used identify subtypes might guide precision therapy.

Language: Английский

---

Pan-cancer proteogenomics characterization of tumor immunity

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1255 - 1277.e27

Published: Feb. 1, 2024

Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%–20% cases have demonstrated durable responses from immune checkpoint blockade. To enhance efficacy immunotherapies, combination therapies suppressing multiple evasion mechanisms are increasingly contemplated. better understand cell surveillance and diverse tumor tissues, we comprehensively characterized landscape more 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct subtypes based on integrative learning type compositions pathway activities. then thoroughly categorized unique genomic, epigenetic, transcriptomic, proteomic changes associated with each subtype. Further leveraging deep phosphoproteomic data, studied kinase activities subtypes, which revealed potential subtype-specific therapeutic targets. Insights this work will facilitate development future strategies precision targeting existing agents.

Language: Английский

---

Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 759 - 779.e12

Published: May 1, 2024

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status a patient's immune system has hindered wider adoption immunoprofiling treatment monitoring response prediction in cancer patients. To address this unmet need, we developed an platform that uses multiparameter flow cytometry to characterize cell heterogeneity peripheral blood healthy donors patients with advanced cancers. Using unsupervised clustering, identified five immunotypes unique distributions different types gene expression profiles. An independent analysis 17,800 open-source transcriptomes same approach corroborated these findings. Continuous immunotype-based signature scores were correlate systemic immunity patient responses treatments, including immunotherapy, prognostically predictively. Our findings illustrate potential utility simple test as flexible tool stratifying into therapy groups based on immunoprofiling.

Language: Английский

---

Multi-omic profiling of follicular lymphoma reveals changes in tissue architecture and enhanced stromal remodeling in high-risk patients

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(3), P. 444 - 463.e10

Published: Feb. 29, 2024

Language: Английский

---

Liquid biopsy for human cancer: cancer screening, monitoring, and treatment

MedComm, Journal Year: 2024, Volume and Issue: 5(6)

Published: May 28, 2024

Currently, tumor treatment modalities such as immunotherapy and targeted therapy have more stringent requirements for obtaining growth information require accurate easy-to-operate detection methods. Compared with traditional tissue biopsy, liquid biopsy is a novel, minimally invasive, real-time tool detecting directly or indirectly released by tumors in human body fluids, which suitable the of new modalities. Liquid has not been widely used clinical practice, there are fewer reviews related applications. This review summarizes applications components (e.g., circulating cells, DNA, extracellular vesicles, etc.) tumorigenesis progression. includes development process techniques biopsies, early screening tumors, detection, guiding therapeutic strategies (liquid biopsy-based personalized medicine prediction response). Finally, current challenges future directions proposed. In sum, this will inspire researchers to use technology promote realization individualized therapy, improve efficacy provide better options patients.

Language: Английский

---

Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(5), P. 766 - 785

Published: Feb. 6, 2024

Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab 5-FU/platinum GEA. Using serial biopsy primary tumor at baseline, after one cycle 5-FU/platinum, addition pembrolizumab, transcriptionally profiled 358,067 single cells identify evolving multicellular microenvironment (TME) networks. Chemotherapy induced early on-treatment hubs with tumor-reactive T-cell M1-like macrophage interactions slow progressors. Faster progression featured increased MUC5A MSLN containing treatment resistance programs M2-like macrophages immunosuppressive stromal interactions. After observed CD8 infiltration development an immunity hub involving CXCL13 program epithelial interferon-stimulated gene programs. Strategies drive increases antitumor immune formation could expand portion patients benefiting from anti-PD-1 approaches.

Language: Английский

---