B cells secrete GABA, which provokes a pro-tumor immune microenvironment

Cancer Cell ◽  
2021 ◽  
Author(s):  
Mara Gilardi ◽  
Monika Ramos ◽  
Daniel Hollern
Keyword(s):  
B Cells ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

scholarly journals Screening of tumor microenvironment-related prognostic genes in breast cancer by data mining

2020 ◽  
Author(s):  
Yunhui LI ◽  
Na REN
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
B Cells ◽  
Memory T Cells ◽  
Immune Therapy ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Immune Score

Abstract Background Accumulating evidence has demonstrated that the components of tumor immune microenvironment (TME) play important roles in breast cancer (BC) initiation, progression and prognosis. Materials and methods We downloaded the TCGA, GSE12276, GSE58812 and GSE42568 datasets. We calculated the immune scores and tumor immune infiltrating cells (TIICs) of TCGA-BRCA and GEO datasets using ESTIMATE and CIBERSORT algorithm, respectively. Then, the overlapping immune-related differentially expressed genes (DEGs) were screened using R ‘limma ’ package between TCGA and GSE12276 datasets. The GO and KEGG enrichment analysis were used to predict the function and signaling pathways of common DEGs. Finally, we extracted a series of tumor immune microenvironment-related genes, and explore the relationship between these genes and clinical outcomes in TCGA, GSE58812 and GSE42568 datasets. Results Based on the ESTIMATE algorithm, the immune scores were significantly associated with cancer types, as well as overall survival in BC patients. The fractions of some TIICs, such asnaïve B cells, memory B cells, CD8 + T cells, resting CD4 + memory T cells, activated CD4 + memory T cells, resting NK cells, monocytes, macrophage M0, M1, M2, resting DCs, activated DCs and resting mast cells, were significantly different between low and high immune score groups (all P <0.05). The DEGs between low and high immune score groups were mainly involved in immune-related biological processes, including adaptive immune response, innate response and inflammatory response. Finally, we found that ACSL5, GIMAP2, HLA-DRA and CLEC10A were significantly associated with prognosis among TCGA, GASE58812 and GSE42568 datasets (all P <0.05). Conclusion These findings provide a more comprehensive understanding of immune cells and immune-related genes within TME as well as prognosis-related genes in BC. Future studies need to perform in vivo and in vitro experiments to clarify the mechanisms of these genes in TME and provide a comprehensive idea to immune therapy.

scholarly journals Increased Tumor Immune Microenvironment CD3+ and CD20+ Lymphocytes Predict a Better Prognosis in Oral Tongue Squamous Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Raísa Sales de Sá ◽  
Marisol Miranda Galvis ◽  
Bruno Augusto Linhares Almeida Mariz ◽  
Amanda Almeida Leite ◽  
Luciana Schultz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Oral Tongue ◽  
Immune Microenvironment ◽  
Independent Prognostic Marker ◽  
Tumor Immune Microenvironment ◽  
Cell Subpopulations

Background: Oral tongue squamous cell carcinoma (OTSCC) causes over 350,000 cases annually and particularly impacts populations in developing countries. Smoking and alcohol consumption are major risk factors. Determining the role of the tumor immune microenvironment (TIME) in OTSCC outcomes can elucidate immune mechanisms behind disease progression, and can potentially identify prognostic biomarkers.Methods: We performed a retrospective study of 48 OTSCC surgical specimens from patients with tobacco and alcohol exposures. A panel of immunoregulatory cell subpopulations including T (CD3, CD4, CD8) and B (CD20) lymphocytes, dendritic cells (CD1a, CD83), macrophages (CD68), and immune checkpoint molecules programmed cell death protein 1 (PD-1) and ligand 1 (PD-L1) were analyzed using immunohistochemistry. The levels of immune effector cell subpopulations and markers were analyzed in relation to overall survival.Results: Pathological characteristics of the tumor microenvironment included inflammatory infiltrates (83.3%), desmoplasia (41.6%), and perineural invasion (50.0%). The TIME contained high levels of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+), as well as immature (CD1a) and mature (CD83) dendritic cells, PD-1, and PD-L1. Higher numbers of TIME infiltrating CD3+ T cells and CD20+ B cells were predictive of better survival, while higher levels of CD83+ mature dendritic cells predicted better survival. CD3+ T cells were identified as an independent prognostic marker for OTSCC. Lastly, CD3+ T cells were strongly correlated with the number of CD8+ cells and PD-L1 expression.Conclusion: Our findings provide evidence that the TIME profile of OTSSC impacted prognosis. The high expression of CD3+ T cells and B cells are predictive of better overall survival and indicative of an immunologically active, inflammatory TIME in patients with better survival. The number of CD3+ T cells was an independent prognostic marker.

Utilizing quantitative multiplex immunofluorescence to characterize paracrine interactions within the tumor-immune landscape of metastatic melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15184-e15184
Author(s):  
Rachel L. Maus ◽  
Alexey Leontovich ◽  
Raymond Moore ◽  
Wendy Kay Nevala ◽  
Thomas J. Flotte ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Metastatic Melanoma ◽  
Immune Reactivity ◽  
Cellular Composition ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Treatment Naïve ◽  
Clinical Responses ◽  
Tumor Infiltrate

e15184 Background: Clinical responses to anti-PD1 immunotherapy in patients with metastatic melanoma (MM) remain challenging to predict. This clinical heterogeneity is also reflected in the tumor-immune microenvironment among patients and within a single tumor lesion. With the emergence of multiplex imaging platforms, defining complex phenotypes at single cell resolution has become possible. Here, we sought to objectively quantify paracrine tumor-immune interactions contributing to the variable clinical responses observed in patients receiving anti-PD1 therapy. Methods: Excisional lymph node (LN) biopsies were obtained from treatment-naïve patients with MM who underwent subsequent anti-PD1 therapy. A single 5µm section of LN tissue was used to assess a 42 analyte panel by multiplex immunofluorescence. From 30 LN samples, 418 fields of view (FOVs) were selected resulting in 14,360 high-resolution images of 4 anatomical subregions: tumor core, tumor-immune interface, tumor infiltrate and adjacent immune stroma. Following image processing, we developed an adaptive classification for tumor-centric cellular neighborhoods (TCCN) to identify and quantify critical paracrine interactions within the tumor-immune microenvironment. Results: Stratification based on responsiveness to anti-PD1 therapy resulted in 4 complete responders (CR) and 12 non-responders (NR) at 12-week follow-up. From 126 FOVs, we defined the cellular composition of 197,865 TCCN across patients based on clinical response and LN subregions. Overall, the percentage of TCCN devoid of any T cells, B cells or macrophages was significantly higher in NR compared to CR irrespective of subregion. However, other markers differentiated TCCN based on subregion. Specifically in CR, tumor core regions were enriched for CD8 T cells, while enrichment for B cells and endothelial cells was demonstrated at the tumor-immune interface. Strikingly, tumor infiltrate regions demonstrate robust immune reactivity with enrichment for M1 polarized macrophages, NK cells and B cells in CR compared to NR. Complete data from the 30 patient cohort across 418 FOVs will be presented. Conclusions: Taken together, this data suggests cellular composition of TCCN across subregions of the LN is dynamic within a single metastatic site. In this small cohort, we introduce a formalized stratification to quantify and classify critical paracrine interactions within the immune-tumor microenvironment with the potential to inform clinical responsiveness to therapy.

NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy

2020 ◽  
Author(s):  
zhihong sun ◽  
Guanjun Deng ◽  
Xinghua Peng ◽  
Xiuli Xu ◽  
Lanlan Liu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Photothermal Therapy ◽  
Whole Body ◽  
Mature Dendritic Cell ◽  
Immune Microenvironment ◽  
Highly Efficient ◽  
Tumor Immune Microenvironment ◽  
Shock Proteins ◽  
Mild Temperature ◽  
Broad Interest

Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination.

Impact of Stimulator of Interferon Genes (STING) Signaling on the Tumor Immune Microenvironment

2020 ◽  
Author(s):  
Ling-Ling Zhu ◽  
Ze-Long Liu ◽  
Jing-Hua Liu ◽  
Zi-han Qu ◽  
Hong-e Zhang ◽  
...  
Keyword(s):  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

A pan-cancer analysis of the human tumor coagulome and its link to the tumor immune microenvironment

2020 ◽  
Author(s):  
Zuzana Saidak ◽  
Simon Soudet ◽  
Marine Lottin ◽  
Valéry Salle ◽  
Marie-Antoinette Sevestre ◽  
...  
Keyword(s):  
Human Tumor ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

scholarly journals Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma

2021 ◽  
Author(s):  
Chao Wang ◽  
Min Shi ◽  
Lei Zhang ◽  
Jun Ji ◽  
Ruyan Xie ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Genomic Analysis ◽  
Molecular Characteristics ◽  
Immune Microenvironment ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Immune Microenvironment ◽  
Genetic Features ◽  
Multiple Recurrences

Abstract Objective To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). Methods The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. Results High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. Conclusions The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.

scholarly journals Characterizing the Tumor Immune Microenvironment with Tyramide-Based Multiplex Immunofluorescence

2020 ◽  
Vol 25 (4) ◽  
pp. 417-432
Author(s):  
Hidetoshi Mori ◽  
Jennifer Bolen ◽  
Louis Schuetter ◽  
Pierre Massion ◽  
Clifford C. Hoyt ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Multispectral Imaging ◽  
Imaging System ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Manual Processing ◽  
Cell Densities ◽  
Immune Profiling

AbstractMultiplex immunofluorescence (mIF) allows simultaneous antibody-based detection of multiple markers with a nuclear counterstain on a single tissue section. Recent studies have demonstrated that mIF is becoming an important tool for immune profiling the tumor microenvironment, further advancing our understanding of the interplay between cancer and the immune system, and identifying predictive biomarkers of response to immunotherapy. Expediting mIF discoveries is leading to improved diagnostic panels, whereas it is important that mIF protocols be standardized to facilitate their transition into clinical use. Manual processing of sections for mIF is time consuming and a potential source of variability across numerous samples. To increase reproducibility and throughput we demonstrate the use of an automated slide stainer for mIF incorporating tyramide signal amplification (TSA). We describe two panels aimed at characterizing the tumor immune microenvironment. Panel 1 included CD3, CD20, CD117, FOXP3, Ki67, pancytokeratins (CK), and DAPI, and Panel 2 included CD3, CD8, CD68, PD-1, PD-L1, CK, and DAPI. Primary antibodies were first tested by standard immunohistochemistry and single-plex IF, then multiplex panels were developed and images were obtained using a Vectra 3.0 multispectral imaging system. Various methods for image analysis (identifying cell types, determining cell densities, characterizing cell-cell associations) are outlined. These mIF protocols will be invaluable tools for immune profiling the tumor microenvironment.

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