Accounting for B-cell behavior and sampling bias predicts anti-PD-L1 response in bladder cancer

2022 ◽  
pp. canimm.0489.2021
Author(s):  
Ilya A Dyugay ◽  
Daniil K Lukyanov ◽  
Maria A Turchaninova ◽  
Ekaterina O Serebrovskaya ◽  
Ekaterina A Bryushkova ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
B Cell ◽  
Sampling Bias ◽  
Cell Behavior

scholarly journals Accounting for B cell behaviour and sampling bias yields a superior predictor of anti-PD-L1 response in bladder cancer

2021 ◽  
Author(s):  
Ilya A Dyugay ◽  
Daniil K Lukyanov ◽  
Maria A Turchaninova ◽  
Andrew R Zaretsky ◽  
Oybek A Khalmurzaev ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Molecular Subtype ◽  
Specific Antigen ◽  
Therapy Response ◽  
Prognostic Indicator ◽  
Molecular Signature ◽  
Cell Functions

Tumor-infiltrating B cells and intratumorally-produced immunoglobulins (IG) play important roles in the tumor microenvironment and response to immunotherapy. IgG antibodies produced by intratumoral B cells may drive antibody-dependent cellular cytotoxicity (ADCC) and enhance antigen presentation by dendritic cells. Furthermore, B cells are efficient antigen-specific antigen presenters that can essentially modulate the behaviour of helper T cells. Here we investigated the role of intratumoral IG isotype and clonality in bladder cancer. Our results show that the IgG1/IgA ratio offers a strong and independent prognostic indicator for the Basal squamous molecular subtype and for the whole ImVigor210 cohort in anti-PD-L1 immunotherapy. Our findings also indicate that effector B cell functions, rather than clonally-produced antibodies, are involved in the antitumor response. High IgG1/IgA ratio was associated with relative abundance of cytotoxic genes and prominence of the IL-21/IL-21R axis suggesting importance of T cell/B cell interaction. We integrated the B, NK, and T cell components, employing immFocus-like normalization to account for the stochastic nature of tumor tissue sampling. Using a random forest model with nested cross-validation, we developed a tumor RNA-Seq-based predictor of anti-PD-L1 therapy response in muscle-invasive urothelial carcinoma. The resulting PRIMUS (PRedIctive MolecUlar Signature) predictor achieves superior sensitivity compared to PD-L1 expression scores or existing gene signatures, allowing for reliable identification of responders even within the desert patient subcohort analyzed as a hold out set.

scholarly journals Kinetics of Human B Cell Behavior and Amplification of Proliferative Responses following Stimulation with IL-21

2006 ◽  
Vol 177 (8) ◽  
pp. 5236-5247 ◽  
Author(s):  
Kim L. Good ◽  
Vanessa L. Bryant ◽  
Stuart G. Tangye
Keyword(s):  
B Cell ◽  
Cell Behavior ◽  
Kinetics Of ◽  
Human B Cell

scholarly journals A robust eleven-genes prognostic model can predict overall survival in bladder cancer patients based on five cohorts

2020 ◽  
Author(s):  
Jiaxing Lin ◽  
Jieping Yang ◽  
Xiao Xu ◽  
Yutao Wang ◽  
Meng Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
High Risk ◽  
B Cell ◽  
Cancer Patients ◽  
Risk Score ◽  
Prognostic Model ◽  
Cell Memory ◽  
Cox Regression Analysis ◽  
B Cell Memory

Abstract Background: Bladder cancer is the tenth most common cancer globally, but existing biomarkers and prognostic models are limited. Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used the least absolute shrinkage and selection operator regression to construct a prognostic Cox model. Kaplan-Meier analysis, receiver operating characteristic curve, and univariate / multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model. Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The 11-genes model could stratify the risk of patients in all five cohorts, and the prognosis was worse in the group with a high-risk score. The area under the curve values of the five cohorts in the first year are all greater than 0.65. Furthermore, this model's predictive ability is stronger than that of age, gender, grade, and T stage. Through the weighted co-expression network analysis, the gene module related to the model was found, and the key genes in this module were mainly enriched in the tumor microenvironment. B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst. Conclusion: The proposed eleven-genes model is a promising biomarker for estimating overall survival in bladder cancer. This model can be used to stratify the risk of bladder cancer patients, which is beneficial to the realization of individualized treatment.

scholarly journals A robust eleven-genes prognostic model can predict overall survival in bladder cancer patients based on five cohorts

2020 ◽  
Author(s):  
Jiaxing Lin ◽  
Jieping Yang ◽  
Xiao Xu ◽  
Yutao Wang ◽  
Meng Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
High Risk ◽  
B Cell ◽  
Cancer Patients ◽  
Risk Score ◽  
Prognostic Model ◽  
Cell Memory ◽  
Cox Regression Analysis ◽  
B Cell Memory

Abstract Background: Bladder cancer is the tenth most common cancer globally, but existing biomarkers and prognostic models are limited. Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used the least absolute shrinkage and selection operator regression to construct a prognostic Cox model. Kaplan-Meier analysis, receiver operating characteristic curve, and univariate / multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model.Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The 11-genes model could stratify the risk of patients in all five cohorts, and the prognosis was worse in the group with a high-risk score. The area under the curve values of the five cohorts in the first year are all greater than 0.65. Furthermore, this model's predictive ability is stronger than that of age, gender, grade, and T stage. Through the weighted co-expression network analysis, the gene module related to the model was found, and the key genes in this module were mainly enriched in the tumor microenvironment. B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst.Conclusion: The proposed eleven-genes model is a promising biomarker for estimating overall survival in bladder cancer. This model can be used to stratify the risk of bladder cancer patients, which is beneficial to the realization of individualized treatment.

Primary Parotid Non-Hodgkin’s B-Cell Lymphoma in an Elderly Woman on Pembrolizumab for Metastatic Invasive Papillary Urothelial Cell Carcinoma of the Bladder

2021 ◽  
pp. 000313482110545
Author(s):  
Bismarck Osumo ◽  
Joseph Radzevich ◽  
Nadia Nashed ◽  
Omar Ustwani ◽  
Gus Slotman
Keyword(s):  
Bladder Cancer ◽  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
Metastatic Cancer ◽  
Cervical Lymphadenopathy ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Metastatic Bladder Cancer ◽  
Response To Chemotherapy

Primary lymphomas of the parotid are rare (4-5%) and seldom appear in patients with pre-existing metastatic cancer from other primary sources. We present a primary marginal zone B-cell lymphoma of the mucosaassociated lymphoid tissue (MALT) in an 84-year-old female with preexisting metastatic bladder cancer. A PET scan that identified positive pelvic/cervical lymphadenopathy and bilateral parotid masses. She underwent transurethral resection of a bladder tumor and started on pembrolizumab chemotherapy. After two years, the left parotid mass decreased in size but the right increased to 3.9cm. Right superficial parotidectomy diagnosed B-Cell Marginal zone lymphoma, staining positive for CD20, PAX5, and Bcl2. pembrolizumab was held and the patient was started on 4 weekly rituximab infusions. A PET scan done 3 months after completion of rituximab showed a good response to chemotherapy. This is the first reported case of a primary parotid gland lymphoma in a patient with active metastatic bladder cancer.

Eosinophilic fasciitis with severe joint contracture in a patient with bladder cancer and B-cell lymphoma

2015 ◽  
Vol 43 (1) ◽  
pp. 68-69 ◽  
Author(s):  
Tomoko Hiraiwa ◽  
Tatsuhiko Mori ◽  
Takenobu Ohashi ◽  
Yuka Hanami ◽  
Toshiyuki Yamamoto
Keyword(s):  
Bladder Cancer ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Joint Contracture ◽  
Eosinophilic Fasciitis

scholarly journals A robust eleven-genes prognostic model can predict overall survival in bladder cancer patients based on five cohorts

2020 ◽  
Author(s):  
Jiaxing Lin ◽  
Jieping Yang ◽  
Xiao Xu ◽  
Yutao Wang ◽  
Meng Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
High Risk ◽  
B Cell ◽  
Cancer Patients ◽  
Prognostic Model ◽  
Cox Regression ◽  
Cell Memory ◽  
Cox Regression Analysis ◽  
B Cell Memory

Abstract Background: Bladder cancer is the tenth most common cancer in the world, but existing biomarkers and prognostic models are limited.Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used selected genes to construct a prognostic model. Kaplan-Meier analysis, Receiver Operating Characteristic curve, and univariate and multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model.Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The model and the 11 genes have excellent performance in predicting overall survival and have been confirmed in 5 cohorts. The model's predictive ability is stronger than other clinical features and has practical significance in clinical application.Through the analysis of the weighted co-expression network, the gene module related to the model was found, and the key genes in this module were mainly enriched in the items related to the tumor microenvironment. When comparing the level of immune cell infiltration in high-risk samples, B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst.Conclusion: The model we developed has strong stability and good performance and can stratify the risk of bladder cancer patients, to achieve individualized treatment.

870 Investigating sexual dimorphism in the tumor immune microenvironment of non-muscle invasive bladder cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A922-A922
Author(s):  
Stephen Chenard ◽  
Chelsea Jackson ◽  
Thiago Vidotto ◽  
Celine Hardy ◽  
Tamara Jamaspishvilli ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Sexual Dimorphism ◽  
B Cell ◽  
Invasive Bladder Cancer ◽  
High Grade ◽  
Immune Microenvironment ◽  
Muscle Invasive Bladder Cancer ◽  
Female Patients ◽  
Tumor Immune Microenvironment ◽  
Muscle Invasive

BackgroundWhile the incidence of non-muscle invasive bladder cancer (NMIBC) is four times higher in men than women, female patients display earlier recurrence than their male counterparts following treatment with Bacillus Calmette-Guerin (BCG) immunotherapy.1 While patient sex (biological differences) and gender (social/behavioral differences) have long been associated with NMIBC incidence and clinical outcome, these factors remain the most understudied phenotypes in biomarker and treatment design.2 We hypothesized that sexual dimorphism in the pre-existing tumor immune microenvironment (TIME) may contribute to the poor clinical outcomes observed in female NMIBC patients.MethodsTo test this hypothesis, we interrogated the expression patterns of genes associated with specific immune cell populations and immune checkpoint pathways using tumor transcriptome profiles from n=460 NMIBC patients (357 males and 103 females). Based on this interrogation, we utilized multiplex immunofluorescence to selectively evaluate the density and spatial distribution of CD79a+ (B), CD163+ (M2-like tumor associated macrophages), and PD-L1+ (programmed death ligand 1) cells in an independent cohort of 510 NMIBC tumors collected from n=390 patients (305 males and 85 females).ResultsWe observed significantly higher expression of immune checkpoints genes CTLA4, PDCD1, TIGIT, LAG3 and ICOS in tumors from female patients. Importantly, transcript levels of the B cell recruiting chemokine CXCL13 and the B cell surface molecule CD40 were significantly increased in tumors from female patients. Multiplex immunofluorescence revealed that CD163+ cells were significantly higher in epithelial and stromal compartments of high-grade tumors (p = 0.0011, p = 0.00034, respectively) from female patients compared to males. While no sex-associated differences were observed in the density of CD79a+ B cells, this population was found to be significantly increased in the epithelial and stromal compartments (p = 6.9e-9, 9.4e-10, respectively) of high-grade tumors compared to low-grade tumors. PD-L1 expression was significantly higher in the epithelial compartment of high-grade tumors from female patients (p = 0.04). Kaplan-Meier survival analysis showed that higher density of CD163+ and CD79a+ cells were independently associated with shorter recurrence free survival (RFS). Notably, these differences in RFS remained in BCG immunotherapy-naïve patients (n=170).ConclusionsThese findings are the first evidence of sexual dimorphism in the TIME of NMIBC and may help to partially explain the worse clinical outcomes experienced by female patients. This study also provides the first evidence of the negative prognostic impact of B cells in NMIBC. Overall, this study provides insight into more rational implementation of immune-based therapies in female NMIBC patients.Ethics ApprovalThis study was approved by the Ethics Review Board at Queen’s University, Kingston, ON, Canada.ReferencesSaginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of bladder cancer. Med Sci 2020;8.Uhlig A, Strauss A, Seif Amir Hosseini A, Lotz J, Trojan L, Schmid M, et al. Gender-specific differences in recurrence of non-muscle-invasive bladder cancer: a systematic review and meta-analysis. Eur Urol Focus 2018;4:924–36.

The Response of Testes Cells to Low Level, Single dose Helium Particle Irradiation

1982 ◽  
Vol 40 ◽  
pp. 252-253
Author(s):  
D.E. Philpott ◽  
W. Sapp ◽  
C. Williams ◽  
J. Stevenson ◽  
S. Black ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Dose ◽  
B Cell ◽  
Cell Survival ◽  
Spermatogonial Stem Cell ◽  
Low Doses ◽  
Particle Irradiation ◽  
Stem Cell Survival ◽  
Irradiation Injury ◽  
Radio Sensitivity

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.

Plasmalemma localisation of inorganic phosphate in B cells pancreas

1978 ◽  
Vol 36 (2) ◽  
pp. 528-529
Author(s):  
F. B. P. Wooding ◽  
K. Pedley ◽  
N. Freinkel ◽  
R. M. C. Dawson
Keyword(s):  
Electron Microscope ◽  
B Cells ◽  
B Cell ◽  
Pancreatic Islets ◽  
High Glucose ◽  
Lead Acetate ◽  
Inorganic Phosphate ◽  
Slight Modification ◽  
Uranyl Acetate ◽  
Lead Phosphate

Freinkel et al (1974) demonstrated that isolated perifused rat pancreatic islets reproduceably release up to 50% of their total inorganic phosphate when the concentration of glucose in the perifusion medium is raised.Using a slight modification of the Libanati and Tandler (1969) method for localising inorganic phosphate by fixation-precipitation with glutaraldehyde-lead acetate we can demonstrate there is a significant deposition of lead phosphate (identified by energy dispersive electron microscope microanalysis) at or on the plasmalemma of the B cell of the islets (Fig 1, 3). Islets after incubation in high glucose show very little precipitate at this or any other site (Fig 2). At higher magnification the precipitate seems to be intracellular (Fig 4) but since any use of osmium or uranyl acetate to increase membrane contrast removes the precipitate of lead phosphate it has not been possible to verify this as yet.

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