Correlation between aryl hydrocarbon receptor and IL‐17 + and Foxp3 + T‐cell infiltration in bladder cancer

2021 ◽  
Author(s):  
Soheila Fattahi ◽  
Monireh Karimi ◽  
Mahdi Ghatreh‐Samani ◽  
Fatemeh Taheri ◽  
Hedayatollah Shirzad ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Infiltration ◽  
Aryl Hydrocarbon ◽  
T Cell Infiltration

scholarly journals ACSL4 Expression Is Associated With CD8+ T Cell Infiltration and Immune Response in Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenjie Luo ◽  
Jin Wang ◽  
Xiaoyan Dai ◽  
Hailiang Zhang ◽  
Yuanyuan Qu ◽  
...  
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
T Cell ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Expression Level ◽  
Cell Infiltration ◽  
Tumor Infiltration ◽  
T Cell Infiltration ◽  
Checkpoint Genes

ObjectiveThis study aimed to explore the role of ACSL4 in CD8+ T cell tumor infiltration and outcomes of bladder cancer (BLCA) patients after immunotherapy.MethodsThe correlation between ACSL4 expression and tumor infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource database. The prognostic significance of ACSL4 in BLCA was analyzed using Kaplan–Meier curves. Immunohistochemistry was used to detect CD8+ T cell infiltration in tumors with high and low ACSL4 expression obtained from patients at the Fudan University Shanghai Cancer Center. The relationships between immune checkpoint genes and immune response were analyzed using The Cancer Genome Atlas and IMvigor 210 cohorts. The molecular functions, cellular components, and biological processes involving ACSL4 were explored using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathway analyses.ResultsThe expression level of ACSL4 was significantly correlated with the infiltration of CD8+ T cells in BLCA tumors (r = 0.192, P = 2.22e-04). Elevated ACSL4 was associated with suppressed tumor progression and better outcomes for BLCA patients. The higher expression level of ACSL4 predicted better immunotherapeutic responses and was associated with higher expression levels of core immune checkpoint genes, including CD274, CTLA4, PDCD1, and LAG3, compared with the low ACSL4 expression group.ConclusionThis study demonstrated for the first time that elevated ACSL4 correlated significantly with CD8+ T cell infiltration and contributed to better immunotherapeutic responses in BLCA patients. Furthermore, ACSL4 serves as a novel biomarker for predicting patient outcomes after immunotherapeutic treatments, which may improve the development of individualized immunotherapy for BLCA.

scholarly journals Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo

2020 ◽  
Vol 8 (2) ◽  
pp. e001673
Author(s):  
Brittany L Bunch ◽  
Jennifer Morse ◽  
Sarah Asby ◽  
Jamie Blauvelt ◽  
Ahmet M Aydin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cellular Therapy ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Tumor Cell Line ◽  
Cell Infiltration ◽  
T Cell Infiltration

BackgroundThe therapeutic armamentarium of bladder cancer has been recently enriched with the introduction of new therapies including immune checkpoint inhibitors, receptor tyrosine kinase inhibitors and antibody drug conjugates, however treatment responses and duration of responses are still less than expected. Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has potential to treat bladder cancer, as previously demonstrated by successful expansion of tumor reactive T cells from human bladder tumors.MethodsA model system using OT-I T cells and an ovalbumin expressing MB49 tumor cell line (MB49OVA) was developed to study ACT in bladder cancer. Systemic ACT-treated mice were given T cells intravenously after lymphodepleting chemotherapy and followed by interleukin (IL)-2 administration. Intravesical ACT treated mice were given T cells directly into the bladder, without chemotherapy or IL-2. TILs were isolated from MB49 orthotopic tumors and expanded ex vivo in IL-2. Immune cell infiltrates were analyzed by flow cytometry. T cell infiltration was studied using a CXCR3 blocking antibody.ResultsSystemic ACT-treated mice had a decrease in tumor growth, increase in T cell infiltration and long-term immune protection compared with control-treated mice. OT-I T cells delivered intravesically were able to control tumor growth without lymphodepleting chemotherapy or IL-2 in MB49OVA orthotopic tumors. Intravesical delivery of TIL expanded from MB49 tumors was also able to decrease tumor growth in mice with MB49 orthotopic tumors. Blocking CXCR3 on OT-I T cells prior to intravesical delivery decreased T cell infiltration into the tumor and prevented the control of tumor growth.ConclusionsThis study demonstrates how TIL therapy can be used in treating different stages of bladder cancer.

scholarly journals High Stroma T-Cell Infiltration is Associated with Better Survival in Stage pT1 Bladder Cancer

2020 ◽  
Vol 21 (21) ◽  
pp. 8407
Author(s):  
Sabine Hülsen ◽  
Eleonora Lippolis ◽  
Fulvia Ferrazzi ◽  
Wolfgang Otto ◽  
Luitpold Distel ◽  
...  
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
T Cell ◽  
Immune Cell ◽  
Negative Impact ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Stage pT1 bladder cancer (BC) shows highly diverse outcomes. Predictive markers are required to stratify patients for personalized treatment. The present study aimed to validate immune response quantification as a prognostic marker. Patients with pT1 BC (n = 167) treated by transurethral resection of the bladder (TURB) were enrolled. Formaldehyde-fixed paraffin-embedded material was stained for CD3 and CD8. Corresponding T cells were counted in three regions with the highest immune response. Numbers of tertiary lymphoid structures (TLS) and lymphocyte aggregates (LA) were quantified. High CD3+ stroma T-cell infiltration was associated with improved survival (p = 0.045), especially in the G3 subgroup (p = 0.01). Cluster with higher immune response showed less recurrence (p = 0.034) and favorable overall survival (OS) (p = 0.019). In contrast, higher CD3+ and CD8+ tumor T-cell infiltration seemed to have a negative impact on prognosis. TLS and LA were more frequently observed in G3 tumors, indicating an increased anti-tumoral immune response. We proved the role of immune cell infiltration and showed that higher infiltration numbers of CD3+ (not CD8+) lymphocytes in the stroma are associated with favorable outcome. Immune cell quantification could be used as a marker to help stratify patients’ risk and therefore, to optimize patients’ management and follow-up examination as well as possible therapies.

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