Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response. DOI Creative Commons

Yonglu Che,

Jinwoo Lee, Farah Abou-Taleb

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Immune checkpoint inhibitors such as anti-PD-1 antibodies (aPD1) can be effective in treating advanced cancers. However, many patients do not respond and the mechanisms underlying these differences remain incompletely understood. In this study, we profile a cohort of with locally-advanced or metastatic basal cell carcinoma undergoing aPD-1 therapy using single-cell RNA sequencing, high-definition spatial transcriptomics tumors draining lymph nodes, immunoreceptor profiling, long-term clinical follow-up. We find that successful responses to PD-1 inhibition are characterized by an induction B-cell receptor (BCR) clonal diversity after treatment initiation. These induced BCR clones spatially co-localize T-cell clones, facilitate their activation, traffic alongside them between tumor nodes enhance clearance. Furthermore, validated aPD1-induced predictor response larger glioblastoma, melanoma, head neck squamous patients, suggesting is generalizable across types discover pre-treatment harbor characteristic gene expression signature portends higher probability inducing therapy, develop machine learning model predicts PD-1-induced from baseline sequencing. findings underscore dynamic role B during immunotherapy, highlighting its importance prognostic marker potential target for intervention non-responders.

Language: Английский

The comprehensive potential of AQP1 as a tumor biomarker: evidence from kidney neoplasm cohorts, cell experiments and pan-cancer analysis DOI Creative Commons
Yifan Liu,

Donghao Lyu,

Yuntao Yao

et al.

Human Genomics, Journal Year: 2025, Volume and Issue: 19(1)

Published: Feb. 23, 2025

Language: Английский

Citations

1
A melanoma brain metastasis CTC signature and CTC:B cell clusters associate with secondary liver metastasis: a melanoma brain-liver metastasis axis DOI Creative Commons
Tetiana Y. Bowley,

Mireya C. Ortiz,

Irina V. Lagutina

et al.

Cancer Research Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Melanoma brain metastasis (MBM) is linked to dismal prognosis, low overall survival, and detected in up 80% of patients at autopsy. Circulating tumor cells (CTCs) are the smallest functional units cancer precursors fatal metastasis. We previously employed an unbiased multilevel approach discover a unique ribosomal protein large/small subunits (RPL/RPS) CTC gene signature associated with MBM. Here, we hypothesized that CTC-driven MBM secondary (“metastasis metastasis” per clinical scenarios), has targeted organ specificity for liver. injected parallel cohorts immunodeficient newly-developed humanized NBSGW (HuNBSGW) mice from CTC-derived identify metastatic patterns. found presence melanoma brain-liver axis mice. Further, RNA-Seq analyses tissues showed significant upregulation RPL/RPS spread Additional CTCs HuNBSGW blood revealed extensive clustering human B these CTC:B cell clusters were also upregulated primary patients, maintained either or promoting liver CTC-generated interrogated single-cell expression levels (10x Genomics Xenium HALO spatial biology platforms, respectively). Collectively, our findings suggest heterotypic interactions can be critical multiple stages

Language: Английский

Citations

0
Comprehensive single-cell atlas of colorectal neuroendocrine tumors with liver metastases: unraveling tumor microenvironment heterogeneity between primary lesions and metastases DOI Creative Commons

Yiqiao Deng,

Qichen Chen,

Chengyao Guo

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 21, 2025

Colorectal neuroendocrine tumors with liver metastases (CRNELM) are associated a poorer prognosis compared to their nonmetastatic counterparts. A comprehensive understanding of the tumor microenvironment (TME) heterogeneity between primary lesions (PL) and (LM) could provide crucial insights for enhancing clinical management strategies these patients. We utilized single-cell RNA sequencing analyze fresh tissue samples from CRNELM patients, aiming elucidate variations in TME PL LM. Complementary multidimensional validation was achieved through spatial transcriptomics, bulk sequencing, multiplex immunohistochemistry/immunofluorescence. Our analysis revealed that LM harboured higher proportion CD8 + T cells, CD4 NK NKT B cells exhibiting stress-like phenotype PL. RGS5 pericytes may play role observed immune within MCs (PL_MCs) (LM_MCs) exhibit distinct activation tumor-associated signaling pathways. Notably, COLEC11 matrix cancer-associated fibroblasts (COLEC11_mCAFs) were found be significantly LM_MCs. Cell communication unveiled potential targetable receptor-ligand interactions COLEC11_mCAFs Multidimensional confirmed prominence characteristic phenotypes, including HSPA6_CD8_Tstr, HSPA6_NK, Moreover, abundance correlated survival rates patient cohort. Overall, our study provides first cellular molecular differences identified cell subsets drive discrepancies support metastatic growth. These highlight therapeutic targets inform better managing

Language: Английский

Citations

0
Age-dependent differences in breast tumor microenvironment: challenges and opportunities for efficacy studies in preclinical models DOI Creative Commons
Paolo Falvo,

Stephan Gruener,

Stefania Orecchioni

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Immunity suffers a function deficit during aging, and the incidence of cancer is increased in elderly. However, most models employ young mice, which are poorly representative adult patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine generation TCF1 + -stem-cell-like T cells (scTs) cyclophosphamide significantly improved anti-PD-1 efficacy anti-PD1-resistant like Triple-Negative Breast Cancer (TNBC) Non-Hodgkin’s Lymphoma (NHL), due to T-cell-mediated tumor killing. Here, we describe effect TT on TNBC growth tumor-microenvironment (TME) (6–8w, human puberty) versus (12 m, 40y-humans) mice. TT-efficacy was similar adults, as CD8 scTs were only marginally reduced adults. single-cell analyses revealed major differences TME: adults had fewer CD4 scTs, B-naïve NK-cells, more memory-B-cells. Cancer-associated-fibroblasts (CAF) with an Extracellular Matrix (ECM) deposition-signature (Matrix-CAFs) common while pro-inflammatory stromal populations myofibroblasts represented Matrix-CAFs mice displayed decreased ECM-remodeling abilities, collagen deposition, different pattern interactions other TME. Taken together, our results suggest age-dependent TME should be considered when designing preclinical studies.

Language: Английский

Citations

0
Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer DOI Open Access

Andreea-Raluca Cozac-Szőke,

Dan Alexandru Cozac, Anca Negovan

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1156 - 1156

Published: Jan. 29, 2025

Gastric cancer (GC) ranks as the fifth most prevalent malignant neoplasm globally, with an increased death rate despite recent advancements in research and therapeutic options. Different molecular subtypes of GC have distinct interactions immune system, impacting tumor microenvironment (TME), prognosis, reaction to immunotherapy. Tumor-infiltrating lymphocytes (TILs) TME are crucial for preventing growth metastasis, evidenced by showing that patients who a significant density TILs better survival rates. But cells evolved variety mechanisms evade surveillance, both sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) Programmed Death-Ligand 1 (PD-L1) playing pivotal role development immunosuppressive TME. They prevent T cell activation proliferation resulting decrease system’s capacity recognize eliminate cells. These checkpoint molecules function via different but complementary mechanisms, expression Siglec-15 being mutually exclusive PD-L1 and, therefore, providing approach. The review explores how affect patient outcomes GC, particular emphasis on their within potential targeting pathways

Language: Английский

Citations

0
Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer DOI Creative Commons
Yasunobu Mano, Yuka Igarashi,

KEISUKE KOMORI

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

The omentum is a common site of peritoneal metastasis in various cancers, including gastric cancer. It contains immune cell aggregates known as milky spots, which provide microenvironment for immunity by regulating innate and adaptive responses. In this study, we investigated gene expression profiles cells from omental spots patients with cancer (n = 37) RNA sequencing analysis classified the into four groups (G1-4). Notably, significant differences were observed between terms macroscopic type, lymphatic invasion, venous pathological stage (pStage). G3, was enriched genes related to acquired immunity, showed earlier tumor stages (macroscopic type 0, Ly0, V0, pStage I) better prognosis. contrast, G4 enrichment neutrophils immunity; G1 G2 no or immune-related genes, suggesting an desert microenvironment. Cytometric revealed significantly more T B fewer G3. Accordingly, may vary depending on progression. When univariate Cox proportional hazards regression models used search prognostically relevant specific 23 potential prognostic identified associated relapse-free survival overall survival. addition, multivariate model using these clinicopathological information that combining marker CD19 Ly had high predictive accuracy Based study’s results, it possible progression, such and/or infiltration cells, affect composition proportions help predict

Language: Английский

Citations

0
B cells in non-lymphoid tissues DOI
Abrar Samiea,

George Celis,

Rashi Yadav

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

Citations

0
Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma DOI Creative Commons
Dylan T. Ammons, R. Adam Harris, Lyndah Chow

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 11, 2025

Abstract Immune cells play key roles in host responses to malignant tumors. The selective pressure that immune elicit on tumors promotes escape, while tumor-associated modulation of creates an environment favorable tumor growth and progression. In this study we used publicly available single-cell RNA sequencing (scRNA-seq) data from the translationally relevant canine osteosarcoma (OS) model compare tumor-infiltrating circulating leukocytes. Through computational analysis investigated differences cell type proportions how OS TME impacted infiltrating transcriptomic profiles relative Differential abundance revealed increased follicular helper T cells, regulatory mature dendritic (mregDCs) TME. gene expression identified exhaustion markers (LAG3, HAVCR2, PDCD1) be upregulated CD4 CD8 within Comparisons B enrichment protein processing endoplasmic reticulum pathways, suggesting were activated following infiltration. Gene changes myeloid suppressive molecules (CD274, OSM, MSR1) TME, indicating skews toward immunosuppressive phenotype. human literature scRNA-seq conserved infiltration, also identifying species differences. Overall, presented here provides new insights into impacts transcriptional programs major populations dogs acts as a resource for comparative immuno-oncology research.

Language: Английский

Citations

0
Artificial intelligence-powered precision: unveiling the tumor microenvironment for a new frontier in personalized cancer therapy DOI Creative Commons

Songwei Feng,

Yin Xia, Yang Shen

et al.

Intelligent Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Literature-scaled immunological gene set annotation using AI-powered immune cell knowledge graph (ICKG) DOI Open Access
Shan He, Yukun Tan, Qing Ye

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Large scale application of single-cell and spatial omics in models patient samples has led to the discovery many novel gene sets, particularly those from an immunotherapeutic context. However, biological meaning sets been interpreted anecdotally through over-representation analysis against canonical annotation databases limited complexity, granularity, accuracy. Rich functional descriptions individual genes immunological context exist literature but are not semantically summarized perform set analysis. To overcome this limitation, we constructed immune cell knowledge graphs (ICKGs) by integrating over 24,000 published abstracts recent using large language (LLMs). ICKGs effectively integrate across individual, peer-reviewed studies, enabling accurate, verifiable graph-based reasoning. We validated quality data obtained independently cytokine stimulation, CRISPR knock-out, protein-protein interaction experiments. Using ICKGs, achieved rich, holistic, accurate including that were unannotated existing approaches use for clinical applications. created interactive website ( https://kchen-lab.github.io/immune-knowledgegraph.github.io/ ) ICKG-based annotations visualize supporting rationale.

Language: Английский

Citations

0