Chemokines and chemokine receptors in colorectal cancer; multifarious roles and clinical impact

Braoudaki, Maria; Ahmad, Mohammed Saqif; Mustafov, Denis; Seriah, Sara; Siddiqui, Mohammad Naseem; Siddiqui, Shoib Sarwar

doi:10.1016/j.semcancer.2022.06.002

Cited by 27 publications

(18 citation statements)

References 118 publications

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“…CXCL16, a chemokine which recruits T cells, was elevated during GCPM ( p = 5.9e-5), consistent with the change in the proportion of T cells, while the concentrations of chemokines that recruit macrophages/monocytes displayed complex changes (Supplementary Fig. 1g ) 25 – 27 . The concentration of CCL5 ( p = 0.0004) was reduced, but CCL2 ( p = 1.6e-5), CCL3 ( p = 0.0125) and CCL4 ( p = 0.0051) were increased during GCPM progression (Supplementary Fig.…”

Section: Resultssupporting

confidence: 58%

“…1g ). The inconsistent changes of the macrophages/monocytes proportions and monocyte-recruitment chemokines may be due to the fact that monocyte-recruitment chemokines can also simultaneously recruit other cells, such as T cells, NK cells, neutrophils, DCs and MDSCs, making the recruitment of monocytes simultaneously influenced by multiple cytokines 25 – 27 . The concentrations of chemokines found via ELISA were consistent with the changes of their transcripts in our scRNA-seq data (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis

Huang

Pang

et al. 2023

Nat Commun

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Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

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Section: Resultssupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis

Huang

Pang

et al. 2023

Nat Commun

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“…Based on TRGs expression, patients with CRC were divided into two TRG clusters. TRG cluster B showed higher survival rates and immune cell infiltration values, and was positively related to CRC-related pathways, including the MAPK 35 , JAK-STAT 36 , and chemokine 37 signaling pathways. The response to anti-checkpoint blockade therapy can be influenced by tumor-infiltrating immune cells, and upregulation of some immunological checkpoint genes, such as PD-1 and CTLA-4 , can be due to tumor-infiltrating CD4 + T cells 38 .…”

Section: Discussionmentioning

confidence: 98%

Identification of novel T cell proliferation patterns, potential biomarkers and therapeutic drugs in colorectal cancer

Wang,

Chan,

Dai

et al. 2024

J. Cancer

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Background: T cells are crucial components of antitumor immunity. A list of genes associated with T cell proliferation was recently identified; however, the impact of T cell proliferation-related genes (TRGs) on the prognosis and therapeutic responses of patients with colorectal cancer (CRC) remains unclear. Methods: 33 TRG expression information and clinical information of patients with CRC gathered from multiple datasets were subjected to bioinformatic analysis. Consensus clustering was used to determine the molecular subtypes associated with T cell proliferation. Utilizing the Lasso-Cox regression, a predictive signature was created and verified in external cohorts. A tumor immune environment analysis was conducted, and potential biomarkers and therapeutic drugs were identified and confirmed via in vitro and in vivo studies. Results: CRC patients were separated into two TRG clusters, and differentially expressed genes (DEGs) were identified. Patient information was divided into three different gene clusters, and the determined molecular subtypes were linked to patient survival, immune cells, and immune functions. Prognosis-associated DEGs in the three gene clusters were used to evaluate the risk score, and a predictive signature was developed. The ability of the risk score to predict patient survival and treatment response has been successfully validated using multiple datasets. To discover more possible biomarkers for CRC, the weighted gene co-expression network analysis algorithm was utilized to screen key TRG variations between groups with high- and low-risk. CDK1 , BATF , IL1RN , and ITM2A were screened out as key TRGs, and the expression of key TRGs was confirmed using real-time reverse transcription polymerase chain reaction. According to the key TRGs, 7,8-benzoflavone was identified as the most significant drug molecule, and MTT, colony formation, wound healing, transwell assays, and in vivo experiments indicated that 7,8-benzoflavone significantly suppressed the proliferation and migration of CRC cells. Conclusion: T cell proliferation-based molecular subtypes and predictive signatures can be utilized to anticipate patient results, immunological landscape, and treatment response in CRC. Novel biomarker candidates and potential therapeutic drugs for CRC were identified and verified using in vitro and in vivo tests.

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“…Traditionally, it has been difficult to model and study tumor-immune system interactions and how immune cells react to drugs and therapeutics ex vivo. Through techniques such as adoptive cell-transfer therapy, tumor and immune cell co-cultures, and humanized mice, PDX and organoid models are increasingly being utilized to study CRC tumor-immune interactions as well as identifying immunotherapy targets in the NF-κB signaling pathway [ 65 , 91 , 92 , 93 , 94 ]. Humanized mice models, highly immunodeficient mice engrafted with functional human immune systems and PDXs or organoids, in particular, are emerging as models for developing and testing immunotherapeutic strategies and have provided many insights into the behaviors of diverse cancers within their native TMEs.…”

Section: Research Models Crcmentioning

confidence: 99%

Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment

Alipourgivi,

Motolani,

Qiu

et al. 2023

IJMS

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Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC—the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.

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Chemokines and chemokine receptors in colorectal cancer; multifarious roles and clinical impact

Cited by 27 publications

References 118 publications

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis

Identification of novel T cell proliferation patterns, potential biomarkers and therapeutic drugs in colorectal cancer

Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment

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