Tertiary lymphoid structures and B cells: An intratumoral immunity cycle

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2254 - 2269

Published: Sept. 11, 2023

Language: Английский

---

Activation of human endogenous retroviruses and its physiological consequences

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 212 - 222

Published: Oct. 23, 2023

Language: Английский

---

Exploiting the therapeutic implications of KRAS inhibition on tumor immunity

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(3), P. 338 - 357

Published: March 1, 2024

SummaryOver the past decade, RAS oncogenic proteins have transitioned from being deemed undruggable to having two clinically approved drugs, with several more in advanced stages of development. Despite initial benefit KRAS-G12C inhibitors for patients tumors harboring this mutation, rapid emergence drug resistance underscores urgent need synergize these other therapeutic approaches improve outcomes. mutant tumor cells can create an immunosuppressive microenvironment (TME), suggesting increased susceptibility immunotherapies following inhibition. This provides a rationale combining inhibitory drugs immune checkpoint blockade (ICB). However, achieving synergy clinical setting has proven challenging. Here, we explore how understanding impact on TME guide innovative inhibition immunotherapies, review progress both pre-clinical and stages, discuss challenges future directions.

Language: Английский

---

Beyond genetics: driving cancer with the tumour microenvironment behind the wheel

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(4), P. 274 - 286

Published: Feb. 12, 2024

Language: Английский

---

Tertiary lymphoid structures in anticancer immunity

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(9), P. 629 - 646

Published: Aug. 8, 2024

Language: Английский

---

Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(730)

Published: Jan. 17, 2024

Immunotherapy has emerged as a crucial strategy to combat cancer by “reprogramming” patient’s own immune system. Although immunotherapy is typically reserved for patients with high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets new targeted therapies. To comprehensively define tumor-specific and likely patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), easy-to-use open-source computational workflow predict splicing-derived MHC-bound peptides (T cell antigen) unannotated transmembrane proteins altered extracellular epitopes (B antigen). This uses highly accurate deep learning immunogenicity prediction (DeepImmuno) in conjunction algorithms rank the tumor specificity (BayesTS) regulators mis-splicing (RNA-SPRINT). T antigens SNAF were frequently evidenced HLA-presented mass spectrometry (MS) response melanoma. neoantigen burden was attributed coordinated splicing factor dysregulation. Shared found up 90% melanoma, correlated overall survival multiple cohorts, induced reactivity, characterized distinct cells origin amino acid preferences. In addition neoantigens, our B focused pipeline (SNAF-B) identified class neoepitopes, which termed ExNeoEpitopes. ExNeoEpitope full-length mRNA predictions specific validated using long-read isoform sequencing vitro localization assays. Therefore, systematic identification revealed potential shared therapy heterogeneous cancers.

Language: Английский

---

Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(6), P. 1018 - 1047

Published: April 6, 2024

Abstract Understanding the role of tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs treatment-naïve early-stage using imaging mass cytometry TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for plasma B immune-excluded squamous cell carcinomas (LUSC). Immune-low were associated fibroblast barriers immune infiltration. The fourth archetype, characterized by sparse lymphocytes high tumor-associated neutrophil (TAN) infiltration, had spatially separated from vasculature exhibited low intratumor heterogeneity. TAN-high LUSC frequent PIK3CA mutations. tumors harbored recently expanded metastasis-seeding subclones a shorter disease-free survival independent stage. These findings delineate genomic, immune, physical surveillance implicate neutrophil-rich metastasis. Significance: This provides novel insights into organization TME context immunogenicity, heterogeneity, evolution. Pairing evolutionary history resolved suggests mechanistic hypotheses progression metastasis implications outcome treatment. article featured Selected Articles Issue, p. 897

Language: Английский

---

Towards targeting transposable elements for cancer therapy

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(2), P. 123 - 140

Published: Jan. 16, 2024

Language: Английский

---

CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(8), P. 1370 - 1385.e9

Published: Aug. 1, 2024

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- peri-tumor mature TLSs (TLS+) improved clinical outcomes than TLS- Using single-cell-RNA-sequencing spatial-enhanced-resolution-omics-sequencing (Stereo-seq), TLS+ tumors enriched IgG

Language: Английский

---

Tumour mutational burden: clinical utility, challenges and emerging improvements

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(10), P. 725 - 742

Published: Aug. 27, 2024

Language: Английский

---