scholarly journals The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaping Chen ◽  
Xiao Zheng ◽  
Changping Wu
Keyword(s):  
Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Research Progress ◽  
Immune Microenvironment ◽  
Appropriate Treatment ◽  
Tumor Immune Microenvironment ◽  
The Relationship ◽  
Selection Of

Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.

scholarly journals 250 Spatial-transcriptomic analysis of tumor-immune microenvironment in AML patients receiving pembrolizumab and decitabine

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A270-A270
Author(s):  
Chen Zhao ◽  
Abigail Wong-Rolle ◽  
Prajan Divakar ◽  
Katherine Calvo ◽  
Christopher Hourigan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Transcriptomic Analysis ◽  
Inadequate Response ◽  
Immune Microenvironment ◽  
Clinical Center ◽  
Tumor Immune Microenvironment ◽  
Refractory Acute Myeloid Leukemia

BackgroundRelapsed or refractory Acute Myeloid Leukemia (R-AML) is a deadly disease with an inadequate response rate to current treatments. Recent advances in immunotherapy shed light on R-AML, and several clinical trials have shown promising potential for combining immune checkpoint inhibitors (ICIs) with hypomethylating agents. A deeper understanding of the tumor-immune microenvironment in R-AML during combination ICI treatment is urgently needed for developing better therapeutics and stratifying treatment strategies.MethodsTo dissect the tumor-immune interactions in the bone marrow microenvironment, we employed nanoString GeoMx Digital Spatial Profiler (DSP) and performed a spatial-transcriptomic analysis of patients with R-AML who received pembrolizumab and decitabine. We compared the transcriptomic profiles and TCR clonalities of tumor-interacting T cells, bystander T cells, and other cells at baseline, post-pembrolizumab treatment, and post-decitabine, which enable us to identify R-AML’s suppressive immune microenvironment and immune cells’ responses to ICI and hypomethylating agent.ResultsWe obtained the spatial-transcriptomic profiles of T cells, stromal cells, and leukemia cells in patients with R-AML at different treatment points. Our TCR-specific probes were able to track T cell clonal changes during treatments.ConclusionsR-AML harbored a complex tumor immune microenvironment and diverse T cell clonality.AcknowledgementsThis research was supported in part by the Intramural Research Program of the NCI (the Center for Cancer Research), NHLBI, and NIH Clinical Center.Ethics ApprovalThis study is approved by NHLBI IRB.

scholarly journals Bioinorganic hybrid bacteriophage for modulation of intestinal microbiota to remodel tumor-immune microenvironment against colorectal cancer

2020 ◽  
Vol 6 (20) ◽  
pp. eaba1590 ◽  
Author(s):  
Xue Dong ◽  
Pei Pan ◽  
Di-Wei Zheng ◽  
Peng Bao ◽  
Xuan Zeng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
In Vivo Studies ◽  
Host Immune System ◽  
Immune Microenvironment ◽  
Phage Display Technology ◽  
Tumor Immune Microenvironment

Mounting evidence suggests that the gut microbiota contribute to colorectal cancer (CRC) tumorigenesis, in which the symbiotic Fusobacterium nucleatum (Fn) selectively increases immunosuppressive myeloid-derived suppressor cells (MDSCs) to hamper the host’s anticancer immune response. Here, a specifically Fn-binding M13 phage was screened by phage display technology. Then, silver nanoparticles (AgNP) were assembled electrostatically on its surface capsid protein (M13@Ag) to achieve specific clearance of Fn and remodel the tumor-immune microenvironment. Both in vitro and in vivo studies showed that of M13@Ag treatment could scavenge Fn in gut and lead to reduction in MDSC amplification in the tumor site. In addition, antigen-presenting cells (APCs) were activated by M13 phages to further awaken the host immune system for CRC suppression. M13@Ag combined with immune checkpoint inhibitors (α-PD1) or chemotherapeutics (FOLFIRI) significantly prolonged overall mouse survival in the orthotopic CRC model.

scholarly journals The role of the tumor microbe microenvironment in the tumor immune microenvironment: bystander, activator, or inhibitor?

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jiayao Ma ◽  
Lingjuan Huang ◽  
Die Hu ◽  
Shan Zeng ◽  
Ying Han ◽  
...  
Keyword(s):  
Immune Cells ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Underlying Mechanisms ◽  
First Time ◽  
Activator Inhibitor ◽  
Stimulation Of

AbstractThe efficacy of cancer immunotherapy largely depends on the tumor microenvironment, especially the tumor immune microenvironment. Emerging studies have claimed that microbes reside within tumor cells and immune cells, suggesting that these microbes can impact the state of the tumor immune microenvironment. For the first time, this review delineates the landscape of intra-tumoral microbes and their products, herein defined as the tumor microbe microenvironment. The role of the tumor microbe microenvironment in the tumor immune microenvironment is multifaceted: either as an immune activator, inhibitor, or bystander. The underlying mechanisms include: (I) the presentation of microbial antigens by cancer cells and immune cells, (II) microbial antigens mimicry shared with tumor antigens, (III) microbe-induced immunogenic cell death, (IV) microbial adjuvanticity mediated by pattern recognition receptors, (V) microbe-derived metabolites, and (VI) microbial stimulation of inhibitory checkpoints. The review further suggests the use of potential modulation strategies of the tumor microbe microenvironment to enhance the efficacy and reduce the adverse effects of checkpoint inhibitors. Lastly, the review highlights some critical questions awaiting to be answered in this field and provides possible solutions. Overall, the tumor microbe microenvironment modulates the tumor immune microenvironment, making it a potential target for improving immunotherapy. It is a novel field facing major challenges and deserves further exploration.

scholarly journals Heparanase (HPSE) Associates with the Tumor Immune Microenvironment in Colorectal Cancer

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1605
Author(s):  
Mengling Liu ◽  
Qing Liu ◽  
Yitao Yuan ◽  
Suyao Li ◽  
Yu Dong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Positive Association ◽  
Immune Microenvironment ◽  
High Expression Group ◽  
Mutation Burden ◽  
Tumor Immune Microenvironment ◽  
Public Datasets

There is an unmet clinical need to identify potential predictive biomarkers for immunotherapy efficacy in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). Heparanase (HPSE) is a multifunctional molecule mediating tumor–host crosstalk. However, the function of HPSE in the tumor immune microenvironment of CRC remains unclear. Data of CRC patients from public datasets (TCGA and GSE39582) and Zhongshan Hospital (ZS cohort) were collected to perform integrative bioinformatic analyses. In total, 1036 samples from TCGA (N = 457), GSE39582 (N = 510) and ZS cohort (N = 69) were included. Samples of deficient MMR (dMMR) and consensus molecular subtypes 1 (CMS1) showed significantly higher HPSE expression. The expression of HPSE also exhibited a significantly positive association with PD-L1 expression, tumor mutation burden and the infiltration of macrophages. Immune pathways were remarkably enriched in the HPSE high-expression group, which also showed higher expressions of chemokines and immune checkpoint genes. Survival analysis suggested that high HPSE expression tended to be associated with shorter overall survival in patients with pMMR mCRC. HPSE might contribute to the immune-activated tumor microenvironment with high levels of immune checkpoint molecules, suggesting that pMMR mCRC with high HPSE expression might respond to immune checkpoint inhibitors.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals Immune-Related Pancytopenia Induced by Anti-PD-1 Therapy – Interrupt or Continue Treatment – The Role of Immunohistochemical Examination

2019 ◽  
Vol 12 (3) ◽  
pp. 820-828 ◽  
Author(s):  
Bożena Cybulska-Stopa ◽  
Andrzej Gruchała ◽  
Maciej Niemiec
Keyword(s):  
Bone Marrow ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Positive Outcomes ◽  
Hematological Disorders ◽  
Therapeutic Outcomes ◽  
Appropriate Treatment ◽  
Programmed Death

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death receptor-1/ligand-1 (anti-PD-1/anti-PD-L1) caused a breakthrough in oncology and significantly improved therapeutic outcomes in cancer patients. ICIs generate a specific reaction in T cells, directed against antigens on cancer cells, leading to their damage and death. Through similar or the same antigens, activated lymphocytes may also have a cytotoxic effect on healthy cells, causing development of specific adverse effects – so-called immune-related adverse events (irAEs). We present the case report of a 56 year old patient with disseminated melanoma. During treatment with immunotherapy (anti PD-1), neutropenic fever and pancytopenia occurred. Trepanobiopsy of the bone marrow was performed to determine the cause of pancytopenia. Histopathological assessment of bone marrow combined with immunophenotype investigations may explain the cause of hematological disorders occurring in the course of treatment with ICIs, and support the choice of an appropriate treatment, directly translated into positive outcomes.

151 - Colonic Bacteria and the Tumor Immune Microenvironment of Colorectal Cancer Patients

2018 ◽  
Vol 154 (6) ◽  
pp. S-41
Author(s):  
Jada C. Domingue ◽  
Nicolas Llosa ◽  
James White ◽  
Julia L. Drewes ◽  
Christine Craig ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Immune Microenvironment ◽  
Colonic Bacteria ◽  
Tumor Immune Microenvironment ◽  
Colorectal Cancer Patients

DE REDACTEUR EN HET BUITENLAND

2019 ◽  
Vol 3 (1) ◽  
pp. 2-27
Author(s):  
Wouter Egelmeers ◽  
Joris Vandendriessche
Keyword(s):  
Creative Process ◽  
General Circulation ◽  
International Level ◽  
Historical Knowledge ◽  
Historical Texts ◽  
Disciplinary Field ◽  
Dutch History ◽  
The Relationship ◽  
Selection Of

IMPORTING TEXTS FROM ABROAD Editors’ reuse of foreign historical texts in Dutch periodicals, 1780-1860 This article explores the ways in which the editors of five Dutch history journals and three magazines for general circulation copied historical texts from abroad, between 1780 and 1860. By comparing original texts with reprinted versions, we show that the editors’ work involved not only ‘passive’ duplication (reprinting in full), but also more active forms of intervention, from the selection of text fragments to their translation, modification or critical review. These varied editorial practices point to a broader creative process through which historical knowledge was tailored to an emerging and nationally-oriented academic audience. Editors here assumed the role of mediators, gatekeepers even in the sense that their judgment determined the very choice of texts. At a time when the study of history was evolving at both the national and international level, and when the relationship between actors making up the disciplinary field was also in flux, editors thus became influential figures.

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