Checkpoint molecules on infiltrating immune cells in colorectal tumor microenvironment

Talaat, Iman M.; Elemam, Noha Mousaad; Zaher, Shroque; Saber-Ayad, Maha

doi:10.3389/fmed.2022.955599

Cited by 10 publications

(10 citation statements)

References 210 publications

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“…Collaboratively generate heat maps for adjuvant use based on different techniques for calculating immune cell infiltration, such as TIMER, 48 quanTIseq, 49 xCell, 50 and EPIC. 51 The expression of immunosuppressive molecules known as immunological checkpoints 52 on immune cells allows for the control of the level of immune activation. Analyzing immune checkpoint genes in tumor tissue can help determine the effectiveness of immunotherapy.…”

Section: Methodsmentioning

confidence: 99%

The exploration of mitochondrial‐related features helps to reveal the prognosis and immunotherapy methods of colorectal cancer

Xie,

Jiang

2023

Cancer Reports

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BackgroundCancer cell survival, proliferation, and metabolism are all intertwined with mitochondria. However, a complete description of how the features of mitochondria relate to the tumor microenvironment (TME) and immunological landscape of colorectal cancer (CRC) has yet to be made.We performed subgroup analysis on CRC patient data obtained from the databases using non‐negative matrix factorization (NMF) clustering. Construct a prognostic model using the mitochondrial‐related gene (MRG) risk score, and then compare it to other models for accuracy. Comprehensive analyses of the risk score, in conjunction with the TME and immune landscape, were performed, and the relationship between the model and different types of cell death, radiation and chemotherapy, and drug resistance was investigated. Results from immunohistochemistry and single‐cell sequencing were utilized to verify the model genes, and a drug sensitivity analysis was conducted to evaluate possible therapeutic medicines. The pan‐cancer analysis is utilized to further investigate the role of genes in a wider range of malignancies.Methods and ResultsWe found that CRC patients based on MRG were divided into two groups with significant differences in survival outcomes and TME between groups. The predictive power of the risk score was further shown by building a prognostic model and testing it extensively in both internal and external cohorts. Multiple immune therapeutic responses and the expression of immunological checkpoints demonstrate that the risk score is connected to immunotherapy success. The correlation analysis of the risk score provide more ideas and guidance for prognostic models in clinical treatment.ConclusionThe TME, immune cell infiltration, and responsiveness to immunotherapy in CRC were all thoroughly evaluated on the basis of MRG features. The comparative validation of multiple queues and models combined with clinical data ensures the effectiveness and clinical practicality of MRG features. Our studies help clinicians create individualized treatment programs for individuals with cancer.

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Section: Methodsmentioning

confidence: 99%

The exploration of mitochondrial‐related features helps to reveal the prognosis and immunotherapy methods of colorectal cancer

Xie,

Jiang

2023

Cancer Reports

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“…The TME is also a cause for concern with plenty of immunosuppressive features at its disposal. This antagonistic milieu can boost CAR T cell exhaustion and limit their persistence, house myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs), repress CAR T cells with abundant immune checkpoint molecules and alter their omics profile [23][24][25][26].…”

Section: Single-cell Analysis Refines Car T Cell Therapymentioning

confidence: 99%

Applications of single‐cell omics for chimeric antigen receptor T cell therapy

Ghaffari,

Saleh,

Akbari

et al. 2023

Immunology

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Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment modality. The breakthroughs in CAR T cell therapy were, in part, possible with the help of cell analysis methods, such as single‐cell analysis. Bulk analyses have provided invaluable information regarding the complex molecular dynamics of CAR T cells, but their results are an average of thousands of signals in CAR T or tumour cells. Since cancer is a heterogeneous disease where each minute detail of a subclone could change the outcome of the treatment, single‐cell analysis could prove to be a powerful instrument in deciphering the secrets of tumour microenvironment for cancer immunotherapy. With the recent studies in all aspects of adoptive cell therapy making use of single‐cell analysis, a comprehensive review of the recent preclinical and clinical findings in CAR T cell therapy was needed. Here, we categorized and summarized the key points of the studies in which single‐cell analysis provided insights into the genomics, epigenomics, transcriptomics and proteomics as well as their respective multi‐omics of CAR T cell therapy.

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“…This interaction downregulates the function of the T cells, preventing them from attacking cancer cells. Similarly, CTLA-4 is a checkpoint molecule expressed on T lymphocytes and plays an inhibitory role by T cell activation after binding to CD80 (also known as B7-1) and CD86 (also known as B7-2), which are located on the antigen-presenting cells (APCs) [4]. Knowing the expression of this pathway may help in indication of check point inhibitor therapy.…”

Section: Pd-1/ctla-4 Receptors Expressionmentioning

confidence: 99%

“…While the genetic and epigenetic status of colorectal cancer cells is crucial for the overall progression of CRC, the tumour microenvironment (TME) that include stroma and resident immune cells, is a constantly changing and dynamic phenomenon that also plays a key role in the initiation and progression of this disease [4]. The TME of CRC is characterized by a unique and complex interplay between cancer cells and immune cells that evolves over time.…”

Section: Introductionmentioning

confidence: 99%

Optimization of a Flow Cytometry Protocol for Pd-1/Ctla-4 Immune Checkpoints Receptors Detection in Colorectal Cancer Tumour Microenvironment

Zamfir¹

2023

FARMACIA

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Considering the individual heterogeneity of the tumours, a personalized approach in oncology is crucial to design a particular dynamic treatment for the individual, from the diagnostic, to monitoring and therapy. In particular, the cellular makeup of the tumour microenvironment consists of diverse immune cells, which include tumour-infiltrating lymphocytes (TILs), as well as tumour-associated macrophages (TAMs) and tumour-associated neutrophils (TANs). These immune cells express various immune checkpoint molecules such as PD-1 and CTLA-4 that play a crucial role in modulating the colorectal cancer microenvironment, controlling the disease's development and response to therapy. Considering the huge potential of PD-1/PD-L1 and CTLA-4 as actionable targets for immunotherapy in colorectal cancer as well as the advantages of the flow cytometry technique, we propose here a flow cytometry method to characterize the colorectal cancer microenvironment in terms of cells populations and their associate immune checkpoint molecular profile. RezumatAvând în vedere heterogenitatea individuală a tumorilor, o abordare personalizată în oncologie este esențială pentru a construi un tratament dinamic individual, pornind de la diagnostic, până la monitorizare și terapie. În mod particular, micromediul tumoral este format din diferite tipuri celulare, printre care și următoarele celule imunitare: limfocite care infiltrează tumorile (tumor infiltrating lymphocytes -TILs), macrofage asociate tumorilor (tumor associated macrophages -TAM) și neutrofile asociate tumorilor (tumor associated neutrophils -TAN). Aceste celule imunitare exprimă diferite molecule de control imun, cum ar fi PD-1 și CTLA-4, care joacă un rol crucial în modularea micromediului tumoral în cancer colorectal, controlând dezvoltarea bolii și răspunsul la terapie. Având în vedere potențialul uriaș al PD-1/PD-L1 și CTLA-4 ca ținte probabile pentru imunoterapia în cancerul colorectal, precum și avantajele tehnicii de citometrie în flux, propunem aici o metodă pentru a caracteriza micromediul tumoral în cancerul colorectal prin citometrie în flux, pentru a evidenția subpopulațiile celulare și profilul lor molecular asociat.

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Checkpoint molecules on infiltrating immune cells in colorectal tumor microenvironment

Cited by 10 publications

References 210 publications

The exploration of mitochondrial‐related features helps to reveal the prognosis and immunotherapy methods of colorectal cancer

The exploration of mitochondrial‐related features helps to reveal the prognosis and immunotherapy methods of colorectal cancer

Applications of single‐cell omics for chimeric antigen receptor T cell therapy

Optimization of a Flow Cytometry Protocol for Pd-1/Ctla-4 Immune Checkpoints Receptors Detection in Colorectal Cancer Tumour Microenvironment

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