Phenotype molding of T cells in colorectal cancer by single‐cell analysis

Di, Jiabo; Liu, Maoxing; Fan, Yingcong; Gao, Pin; Wang, Zaozao; Jiang, Beihai; Su, Xiangqian

doi:10.1002/ijc.32856

Cited by 26 publications

(28 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The enrichment of ICOS, CD45RO, PD-1, programmed death-ligand 1 (PD-L1), lymphocyte-activation gene 3 (LAG-3), CTLA-4, and T-cell immunoglobulin mucin-3 (TIM-3) on BLIMP-1 + regulatory T cells suggested that BLIMP-1 + Treg cells have a more activated phenotype than conventional Treg cells and may play a role in the antitumor immune response. Di et al [ 41 ] also found that exhausted T cells (PD-1 + CD38 + HLA-DR + CCR7 + CD127 – ) and regulatory T cells (CD4 + CD25 + CD127 – ) were increased in tumor tissues. Moreover, they found that CD8 + CD28 – immunosenescent T cells with impaired proliferation capacity were the most abundant T cell population in colorectal tumors.…”

Section: Immune Landscape Of Colorectal Cancersmentioning

confidence: 99%

Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Bae

Yoo

Kim

et al. 2020

J Pathol Transl Med

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third leading cause of cancer-related death in Korea [1]. Because of rapid spread of colonoscopy screening, there was a general decrease in CRC until 2010. However, recent studies have reported that the decline in CRC incidence has reversed during the last few years, especially in middle-aged persons, and the occurrence of early-onset CRC has rapidly increased [2]. Most patients with CRC are diagnosed at an operable stage; however, approximately 20% of patients with stage III or high-risk stage II CRC relapse within 5 years after curative resection [3]. Moreover, the 5-year relative survival rate for metastatic CRC is 14% [2]. To improve clinical outcomes for patients with CRC, a more effective treatment modality is required to fulfill those unmet needs. Cancer is fundamentally a genetic disease since the accumulation of mutations, fusions, and copy number alterations drives tumorigenesis. However, recent research on the tumor immune microenvironment (TIME) has revealed the importance of interactions between tumor cells and surrounding immune cells in tumorigenesis [4]. Immune checkpoint inhibitor (ICI) treatment , such as anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies and anti-programmed death-1 (PD-1) antibodies, has shown marked clinical benefits in many types of cancer [5,6]. CRC also holds promise for cancer immunotherapy use, and the U.S. Food and Drug Administration (U.S. FDA) approved immunotherapeutic agents for microsatellite instability-high (MSI-H) CRC in 2017 (Fig. 1) [7,8]. In this review, we describe the landscape of the immune microenvironment in CRC and summarize the clinical usefulness of several suggested biomarkers in CRC immunotherapy. IMMUNE LANDSCAPE OF COLORECTAL CANCERS Historical use of microscopic evaluation of immune environment in CRCs To our knowledge, Spratt and Spjut [9] published the first study on integrative histologic evaluation of CRCs in 1967. In that study, the authors evaluated histologic grade, mucinous elements, depth of invasion, characteristics of tumor border, lym

show abstract

Section: Immune Landscape Of Colorectal Cancersmentioning

confidence: 99%

Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Bae

Yoo

Kim

et al. 2020

J Pathol Transl Med

View full text Add to dashboard Cite

show abstract

“…Moreover, it has been shown that patients with microsatellite stable (MSS) cancers do not benefit from immunotherapy as microsatellite instable (MSI) cancers (Emambux et al, 2018). In fact, in a recent study, it was shown that the dynamics of the T-cells phenotype differ between MSS and MSI cancers (Di et al, 2020). Future studies should be conducted to correlate the status of microsatellite stability with the functional effects of EVs.…”

Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

Abu

Othman

Razak

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.

show abstract

“…Due to a lack of robust effector functions, exhausted T cells express multiple inhibitory receptors with an altered transcriptional programme ( 25 ). An abundance of exhausted T cells results in an invalid control of tumors, leading to poor prognosis ( 26 – 29 ). Yet, after deconvolution of the TCGA HCC RNA-seq data with CIBERSORTx, the proportion distribution of 11 cell types (mainly six cell types) in tumor and normal tissues showed a different trend.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

Shen

Zhou

et al. 2020

Front. Med.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a commonly diagnosed cancer with high mortality rates. The immune response plays an important role in the progression of HCC. Immunotherapies are becoming an increasingly promising tool for treating cancers. Advancements in scRNA-seq (single-cell RNA sequencing) have allowed us to identify new subsets in the immune microenvironment of HCC. Yet, distribution of these new cell types and their potential prognostic value in bulk samples from large cohorts remained unclear. This study aimed to investigate the tumor-infiltration and prognostic value of new cell subsets identified by a previous scRNA-seq study in a TCGA HCC cohort using CIBERSORTx, a machine learning method to estimate cell proportion and infer cell-type-specific gene expression profiles. We observed different distributions of tumor-infiltrating lymphocytes between tumor and normal cells. Among these, the CD4-GZMA cell subset showed association with prognosis (log-rank test, p < 0.05). We further analyzed CD4-GZMA cell specific gene expression with CIBERSORTx, and found 19 prognostic genes (univariable cox regression, p < 0.05). Finally, we applied Least absolute shrinkage and selection operator (LASSO) Cox regression to construct an immune risk score model and performed a prognostic assessment of our model in TCGA and ICGC cohorts. Taken together, the immune landscape in HCC bulk samples may be more complex than assumed, with heterogeneity and different tumor-infiltration relative to scRNA-seq results. Additionally, CD4-GZMA cells and their characteristics may yield therapeutic benefits in the immune treatment of HCC.

show abstract

Phenotype molding of T cells in colorectal cancer by single‐cell analysis

Cited by 26 publications

References 47 publications

Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

Contact Info

Product

Resources

About