Spatial interaction mapping of PD-1/PD-L1 in Head and Neck Cancer reveals the role of Macrophage-Tumour Barriers associated with immunotherapy response DOI Creative Commons
Vahid Yaghoubi Naei,

Rafael Tubelleza,

James Monkman

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Background Mucosal head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage, where the prognosis poor due to high rates of recurrence metastasis [1]. With approximately one million new cases projected in 2024, worldwide mortality HNSCC estimated reach 50% detected same year [2]. Patients with early-stage tumours showed a 50–60% five-year survival rate US. Immune checkpoint inhibitors (ICIs) have shown promising results prolonging subset patients recurrent or metastatic disease. However, challenges remain, particularly limited efficacy PD-1/PD-L1 blockade therapies. PD-L1 protein expression has been be its predictive power for ICI Emerging evidence shows that intricate characterisation tumour microenvironment (TME) fundamental understand interacting cells. Methods In this study, we sought apply more nuanced approach understanding cellular interactions by mapping across whole-slide tissue samples collected prior therapy. We used combination spatial proteomics (Akoya Biosciences) in situ proximity ligation assay (isPLA, Navinci Diagnostics) visualise types neighbourhoods within TME. Results Our findings indicate existence isPLA+ between macrophages/CD3 T cell-enriched cells tumour-stroma boundaries ICI-resistant tumours. The presence these dense macrophage-tumour layers, which are either absent dispersed responders, indicates barrier may restrict immune infiltration promote escape mechanisms. contrast, responders had abundant B aggregates, predominantly around edges linked enhanced responses therapy better clinical outcomes. Conclusion This study highlights utility isPLA detecting distinct tumour-immune TME, offering interaction metrics stratifying optimising immunotherapy strategies.

Язык: Английский

Combined targeting of senescent cells and senescent macrophages: A new idea for integrated treatment of lung cancer DOI
Ming Gu, Yang Liu, Wenhui Zheng

и другие.

Seminars in Cancer Biology, Год журнала: 2024, Номер 106-107, С. 43 - 57

Опубликована: Авг. 29, 2024

Язык: Английский

Процитировано

11
Advances in Melanoma: From Genetic Insights to Therapeutic Innovations DOI Creative Commons
Fernando Valdez-Salazar,

Luis Alberto Jiménez-Del Río,

Jorge Ramón Padilla‐Gutiérrez

и другие.

Biomedicines, Год журнала: 2024, Номер 12(8), С. 1851 - 1851

Опубликована: Авг. 14, 2024

Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between alterations, such as mutations BRAF, NRAS, KIT, pathogenesis. The MAPK PI3K/Akt/mTOR signaling pathways are highlighted for their roles tumor growth resistance mechanisms. Additionally, this delves impact of epigenetic modifications, including DNA methylation histone changes, on progression. microenvironment, characterized by immune cells, stromal soluble factors, plays a pivotal role modulating behavior treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, AI-driven diagnostics transforming research, offering precise personalized approaches treatment. Immunotherapy, particularly checkpoint inhibitors mRNA vaccines, has revolutionized therapy enhancing body’s response. Despite these advances, mechanisms remain challenge, underscoring need combined therapies ongoing achieve durable comprehensive overview aims highlight current state transformative impacts advancements clinical practice.

Язык: Английский

Процитировано

6
Discovery of a novel small molecule as CD47/SIRPα and PD-1/PD-L1 dual inhibitor for cancer immunotherapy DOI Creative Commons

Shengzhe Jin,

Hongfei Wang, Yang Li

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Март 11, 2024

Abstract Background Targeting the tumor microenvironment (TME) has emerged as a promising strategy in cancer treatment, particularly through utilization of immune checkpoint blockade (ICB) agents such PD-1/PD-L1 inhibitors. Despite partial success, presence tumor-associated macrophages (TAMs) contributes to an immunosuppressive TME that fosters progression, and diminishes therapeutic efficacy ICB. Blockade CD47/SIRPα pathway proven be effective intervention, restores macrophage phagocytosis yields substantial antitumor effects, especially when combined with blockade. Therefore, identification small molecules capable simultaneously blocking interactions remained imperative. Methods SMC18, molecule capacity targeting both SIRPα PD-L1 was obtained using MST. The efficiency SMC18 interrupting tested by assay. function enhancing activity T cells assay co-culture effects mechanisms were investigated MC38-bearing mouse model. Results dual-targets protein, identified. effectively blocked interaction, thereby restoring phagocytosis, disrupted interactions, thus activating Jurkat cells, evidenced increased secretion IL-2. demonstrated inhibition MC38 growths promoting infiltration CD8 + M1-type into sites, while also priming macrophages. Moreover, combination radiotherapy (RT) further improved efficacy. Conclusion Our findings suggested compound which pathways, could candidate for macrophage- T-cell-mediated responses immunotherapy.

Язык: Английский

Процитировано

5
CAR-macrophage: Breaking new ground in cellular immunotherapy DOI Creative Commons

Ting Huang,

Chenqi Bei,

Zhenhua Hu

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Окт. 3, 2024

Chimeric Antigen Receptor (CAR) technology has revolutionized cellular immunotherapy, particularly with the success of CAR-T cells in treating hematologic malignancies. However, have limited efficacy against solid tumors. To address these limitations, CAR-macrophages (CAR-Ms) leverage innate properties macrophages specificity and potency CAR technology, offering a novel promising approach to cancer immunotherapy. Preclinical studies shown that CAR-Ms can effectively target destroy tumor cells, even within challenging microenvironments, by exhibiting direct cytotoxicity enhancing recruitment activation other immune cells. Additionally, favorable safety profile their persistence tumors position as potentially safer more durable therapeutic options compared This review explores recent advancements including engineering strategies optimize anti-tumor preclinical evidence supporting use. We also discuss challenges future directions developing therapies, emphasizing potential revolutionize By harnessing unique macrophages, offer groundbreaking overcoming current limitations cell paving way for effective sustainable treatments.

Язык: Английский

Процитировано

5
Evaluation of the microenvironment formed by interferon-β DOI Creative Commons
Mai Yamagishi, Yutaka Hori,

Nobutake Suzuki

и другие.

Frontiers in Chemical Biology, Год журнала: 2025, Номер 3

Опубликована: Янв. 21, 2025

Heterogeneity in the cellular microenvironment vivo affects variability of reactivity among immune cells. Individual-specific microenvironmental differences play a crucial role determining macroscopic outcomes, such as efficacy immunotherapy and disease progression. The is also featured by cytokines released from cells, significantly regulating cell function. However, overall understanding, at single-cell resolution, how shape promote paracrine signaling remains unclear. In this manuscript, we propose methodology that addresses both itself response to comprehend behavior level. Our objective contribute basic understanding interplay between cells their microenvironment, with particular relevance implications for

Язык: Английский

Процитировано

0
Spatial interaction mapping of PD-1/PD-L1 in head and neck cancer reveals the role of macrophage-tumour barriers associated with immunotherapy response DOI Creative Commons
Vahid Yaghoubi Naei,

Rafael Tubelleza,

James Monkman

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 12, 2025

Abstract Background Mucosal head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage, where the prognosis poor due to high rates of recurrence metastasis. With approximately one million new cases projected in 2024, worldwide mortality HNSCC estimated reach 50% detected same year. Patients with early-stage tumours showed a 50–60% five-year survival rate US. Immune checkpoint inhibitors (ICIs) have shown promising results prolonging subset patients recurrent or metastatic disease. However, challenges remain, particularly limited efficacy PD-1/PD-L1 blockade therapies. PD-L1 protein expression has been be its predictive power for ICI Emerging evidence shows that intricate characterisation tumour microenvironment (TME) fundamental understand interacting cells. This study aims bridge gap understanding tumor by identifying distinct spatial patterns interactions their association immunotherapy responses (HNSCC). Methods In this study, we sought apply more nuanced approach cellular mapping across whole-slide tissue samples collected prior therapy. We used combination proteomics (Akoya Biosciences) situ proximity ligation assay (isPLA, Navinci Diagnostics) visualise types neighbourhoods within TME. Results Our findings indicate existence isPLA + between macrophages/CD3 T cell-enriched cells tumour-stroma boundaries ICI-resistant tumours. The presence these dense macrophage-tumour layers, which are either absent dispersed responders, indicates barrier may restrict immune infiltration promote escape mechanisms. contrast, responders had abundant B aggregates, predominantly around edges linked enhanced therapy better clinical outcomes. Conclusion highlights utility detecting tumour-immune TME, offering interaction metrics stratifying optimising strategies.

Язык: Английский

Процитировано

0
Macrophage-derived lncRNAs in cancer: regulators of tumor progression and therapeutic targets DOI
Muath Suliman, Raed Obaid Saleh,

M Chandra

и другие.

Medical Oncology, Год журнала: 2025, Номер 42(4)

Опубликована: Март 6, 2025

Язык: Английский

Процитировано

0
MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer DOI Creative Commons
Jinmiao Tian, Lichao Zhang, Xiaoqin La

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 5, 2025

The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, exosomes miRNAs they secrete crucial regulation. Our previous study showed that GRP78-induced infinitely tend to be M2-type TAMs. In this study, M0 macrophage were collected co-incubated with colorectal cancer (CRC) cells. results implied induced by GRP78 (GRP78-exos) significantly promoted stemness chemoresistance CRC vitro vivo. Further, top 5 upregulated GRP78-exos obtained from miRNA sequencing data. qRT-PCR validation revealed miR-769-5p was most observably could directly transferred into cells via GRP78-exos. Mechanistically, indicated targeted MAPK1 regulate cell cycle-related proteins RB1, cyclin D1, E1. This contributes entering a quiescent state, which leads development chemoresistance. Moreover, is also expressed higher tissues 5-FU-resistant patients. summary, findings indicate novel function as potential marker for diagnosis treatment chemotherapy resistance CRC.

Язык: Английский

Процитировано

0
Topohistology of dendritic cells and macrophages in the distal and proximal nodes along the lymph flow from the lung DOI Creative Commons
Masaya Aoki, Go Kamimura,

Aya Harada‐Takeda

и другие.

Journal of Anatomy, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Abstract Nodal dendritic cells and CD169‐positive macrophages cross‐present cancer antigens earlier in the proximal nodes than distal along lymph flow from cancer. We examined topohistological differences between before formation of metastasis. Immunohistochemical morphometric analyses were performed to examine DC‐SIGN‐, CD68‐, subcarinal node (proximal) paratracheal (distal nodes) 16 patients with lower‐lobe lung without metastasis (adenocarcinoma, 11; squamous, 5). Nodes at same sites 10 upper‐lobe used as controls. In all nodes, medullary sinus was filled CD68‐positive CD169‐negative macrophages, most which showed anthracosis. The carried a significantly smaller overlap clusters DC‐SIGN‐positive relative ( p = 0.015). Irrespective pathology, tumor size correlated longer subcapsular containing either or 0.003, 0.043). A small these well missing paracortical sinuses evident negative control outside 0.006). Since cells, especially composite overlapped cluster, are likely be derived monocytes, larger tumors appeared accelerate migration into sinus. contrast suggested active status node, have already been suppressed. This downregulation reached level node.

Язык: Английский

Процитировано

0
Oncolytic Vaccinia Virus Armed with GM-CSF and IL-7 Enhances Antitumor Immunity in Pancreatic Cancer DOI Creative Commons
Wenyi Yan,

Yujing Xuan,

Rui Wang

и другие.

Biomedicines, Год журнала: 2025, Номер 13(4), С. 882 - 882

Опубликована: Апрель 5, 2025

Objectives: Pancreatic cancer remains a therapeutic challenge due to its immunosuppressive microenvironment and treatment resistance. This study aimed develop novel recombinant oncolytic vaccinia virus (VVL-GL7) co-expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) interleukin-7 (IL-7), designed enhance anti-tumor immunity synergize with immune checkpoint inhibitors. Methods: VVL-GL7 was constructed through CRISPR/Cas9-mediated knockout of TK A49 genes, combined the simultaneous insertion dual cytokine-encoding cassettes. Anti-tumor efficacy evaluated in vitro vivo using C57BL/6 mouse Syrian hamster pancreatic models. Comprehensive profiling CD8+ T-cell macrophage infiltration dynamics while simultaneously assessing memory differentiation patterns flow cytometry. Preclinical combination studies PD-1 inhibitor were systematically syngeneic model. Results: exhibited potent activity, inducing significant tumor regression both preclinical therapy significantly augmented within microenvironment, concomitantly driving differentiation. The synergistic effects blockade further improved outcomes, resulting higher remission rates compared monotherapy achieving complete Conclusions: reprograms synergizes anti-PD-1 antibodies overcome resistance cancer.

Язык: Английский

Процитировано

0