scholarly journals The Human Microbiomes in Pancreatic Cancer: Towards Evidence-Based Manipulation Strategies?

2021 ◽  
Vol 22 (18) ◽  
pp. 9914
Author(s):  
Giovanni Brandi ◽  
Silvia Turroni ◽  
Florencia McAllister ◽  
Giorgio Frega
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Approaches ◽  
Immune Microenvironment ◽  
Essential Components ◽  
Tumor Immune Microenvironment ◽  
Current Therapies ◽  
Treatment Responses ◽  
The One ◽  
Resistance To Chemotherapy

Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic “hub” interfaced between the gut and the host.

scholarly journals Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer

2021 ◽  
Author(s):  
Inga-Maria Launonen ◽  
Nuppu Lyytikäinen ◽  
Julia Casado ◽  
Ella Anttila ◽  
Angéla Szabó ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Single Cells ◽  
High Grade ◽  
Prognostic Role ◽  
Immune Microenvironment ◽  
Proteomic Data ◽  
Tumor Immune Microenvironment ◽  
Cellular Phenotypes

Abstract The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generated spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes (HRwt). We identified a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we found an opposing prognostic role of a proliferative tumor-cell phenotypic subpopulation in the HR-genotypes, which associated with enhanced spatial tumor-immune interactions by the CD8+ and CD4+T-cells in BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the premise to improve immunotherapeutic strategies and patient stratification in HGSC.

scholarly journals The Immune Microenvironment in Pancreatic Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7307 ◽  
Author(s):  
Magdalena Huber ◽  
Corinna U. Brehm ◽  
Thomas M. Gress ◽  
Malte Buchholz ◽  
Bilal Alashkar Alhamwe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Stroma ◽  
Ductal Adenocarcinoma ◽  
Cancer Type ◽  
Cellular Interactions ◽  
Therapeutic Approaches ◽  
Immune Microenvironment ◽  
Cellular Immune

The biology of solid tumors is strongly determined by the interactions of cancer cells with their surrounding microenvironment. In this regard, pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) represents a paradigmatic example for the multitude of possible tumor–stroma interactions. PDAC has proven particularly refractory to novel immunotherapies, which is a fact that is mediated by a unique assemblage of various immune cells creating a strongly immunosuppressive environment in which this cancer type thrives. In this review, we outline currently available knowledge on the cross-talk between tumor cells and the cellular immune microenvironment, highlighting the physiological and pathological cellular interactions, as well as the resulting therapeutic approaches derived thereof. Hopefully a better understanding of the complex tumor–stroma interactions will one day lead to a significant advancement in patient care.

scholarly journals Sexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Simon Milette ◽  
Masakazu Hashimoto ◽  
Stephanie Perrino ◽  
Shu Qi ◽  
Michely Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Sexual Dimorphism ◽  
Liver Metastases ◽  
Suppressor Cells ◽  
Cytotoxic T Cell ◽  
Immune Microenvironment ◽  
Ovariectomized Mice ◽  
Cell Accumulation ◽  
Tumor Immune Microenvironment

AbstractLiver metastases (LM) remain a major cause of cancer-associated death and a clinical challenge. Here we explore a sexual dimorphism observed in the regulation of the tumor immune microenvironment (TIME) of LM, wherein the accumulation of myeloid-derived suppressor cells (MDSC) and regulatory T cells in colon and lung carcinoma LM is TNFR2-dependent in female, but not in male mice. In ovariectomized mice, a marked reduction is observed in colorectal, lung and pancreatic carcinoma LM that is reversible by estradiol reconstitution. This is associated with reduced liver MDSC accumulation, increased interferon-gamma (IFN-γ) and granzyme B production in CD8+ T cells and reduced TNFR2, IDO2, TDO and Serpin B9 expression levels. Treatment with tamoxifen increases liver cytotoxic T cell accumulation and reduces colon cancer LM. The results identify estrogen as a regulator of a pro-metastatic immune microenvironment in the liver and a potential target in the management of liver metastatic disease.

scholarly journals Identification of Genomic Instability Related Lncrna Signature Associated with Immune Microenvironment in Pancreatic Cancer

2021 ◽  
Author(s):  
Xiaole Zhu ◽  
Rong Yu ◽  
Yunpeng Peng ◽  
Chaoqun Hou ◽  
Chenyuan Shi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Genomic Instability ◽  
Risk Score ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
Immune Microenvironment ◽  
Important Indicator ◽  
Cox Regression Analysis ◽  
Tumor Immune Microenvironment

Abstract Background: Increasing evidence suggested that the critical roles for lncRNAs in the maintenance of genomic stability. However, the identification of genomic instability related lncRNA signature (GILncSig) and their clinical significance in tumor immune microenvironment of pancreatic cancer remain largely unexplored.Methods: In the present study, a systematic analysis of lncRNA expression profiles and somatic mutation profiles was performed in pancreatic cancer patients from TCGA. We performed co-expression network and Gene Ontology (GO) enrichment analyses to determine the potential functions and pathways involved in lncRNAs are associated with genomic instability. We then development a risk score model to describe the characteristics of the model and verify its prediction accuracy. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in pancreatic cancer. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. Results: We identified 206 GILncSig, of which five were screened to develop a prognostic GInLncSig model. Multivariate Cox regression analysis and stratified analysis revealed that the prognostic value of the GILncSig was independent of other clinical variables. ROC analysis suggested that GILncSig is better than the existing lncRNA-related signatures in predicting survival. Additionally, the prognostic performance of the GILncSig was also found to be favorable in patients carrying wild-type KRAS, TP53 and SMAD4. Besides, a nomogram exhibited appreciable reliability for clinical application in predicting the prognosis of patients. Finally, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4, etc.). Conclusion: In summary, the GILncSig identified by us may have crucial role in immune cell infiltration，immunotherapy and important indicator for clinical stratification management and therapy decisions for pancreatic cancer patients.

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