Prognostic significance of immunoscore related markers in bladder cancer

Abstract Background The significance of total and specific subpopulations of tumor-infiltrating lymphocytes (TILs) in cancer is now well-documented. In the present study, we investigated the relevance of CD3+, CD8 +, CD45RO +, and FOXP3 + TILs to the prognosis and survival of patients with bladder c...

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Main Authors: Ali Ariafar, Alireza Sanati, Simin Ahmadvand, Golsa Shekarkhar, Akbar Safaei, Zahra Shayan, Zahra Faghih
Format: Article
Language:English
Published: BMC 2022-08-01
Series:BMC Urology
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Online Access:https://doi.org/10.1186/s12894-022-01085-6
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author Ali Ariafar
Alireza Sanati
Simin Ahmadvand
Golsa Shekarkhar
Akbar Safaei
Zahra Shayan
Zahra Faghih
author_facet Ali Ariafar
Alireza Sanati
Simin Ahmadvand
Golsa Shekarkhar
Akbar Safaei
Zahra Shayan
Zahra Faghih
author_sort Ali Ariafar
collection DOAJ
description Abstract Background The significance of total and specific subpopulations of tumor-infiltrating lymphocytes (TILs) in cancer is now well-documented. In the present study, we investigated the relevance of CD3+, CD8 +, CD45RO +, and FOXP3 + TILs to the prognosis and survival of patients with bladder cancer and the disease's clinical-pathological parameters. Methods Infiltration of each subset was immunohistochemically evaluated in both stromal and intratumoral regions of tumor tissues from 85 patients with urothelial cell carcinoma of the bladder, with known survival. Results Our results indicated that intratumoral CD45RO+ lymphocytes were significantly higher in high-grade tumors than in low-grade ones (P = 0.028). The frequencies of intratumoral CD3+ (P = 0.002), CD8 + (P = 0.008), intratumoral (P = 0.002), and stromal (P = 0.017) CD45RO+ lymphocytes were also higher in patients with muscular invasion than those without invasion. The frequencies of intratumoral CD3+ (P = 0.043), CD8+ (P = 0.003), CD45RO+ (P = 0.023), and total CD45RO+ (P = 0.015), showed variation in patients with different T-stage, as well; mostly increased in T2 versus Ta and T1. Comparing patients in different stages revealed an increase in the frequencies of total CD3+ (P = 0.011), intratumoral CD3+ (P = 0.006), total CD8+ (P = 0.012), intratumoral CD8+ (P = 0.009) and stromal CD8+ (P = 0.034), as well as total and stromal CD45RO+ lymphocytes (P = 0.01 and P = 0.034, respectively) in stage II comparing to stage I, while the frequencies of stromal CD3+ (P = 0.077) and CD8+ (P = 0.053) cells tended to be decreased in stage III compared to stage II. Conclusions We collectively observed that the frequency of immune cells, especially CD45RO+, CD3+, and CD8+ lymphocytes, were significantly higher in early-progressed tumors. This observation could be explained by continuous and prolonged stimulation of immune cells with tumor antigens during tumor progression or an increase in the recruiting factors, especially in the early stages, to eliminate tumor cells. However, with tumor progression to the late stages, the inhibitory microenvironment provided by tumor cells suppresses or changes the functionality of the effector and memory immune cells to help tumor growth. However, more functional studies with larger sample sizes are needed to reveal the real status of the immune system in patients with bladder cancer.
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spelling doaj.art-9950f777e22e4d8e89a451b788bfc1ec2022-12-22T02:23:04ZengBMCBMC Urology1471-24902022-08-012211910.1186/s12894-022-01085-6Prognostic significance of immunoscore related markers in bladder cancerAli Ariafar0Alireza Sanati1Simin Ahmadvand2Golsa Shekarkhar3Akbar Safaei4Zahra Shayan5Zahra Faghih6Department of Urology, School of Medicine, Shiraz University of Medical SciencesDepartment of Urology, School of Medicine, Shiraz University of Medical SciencesShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical SciencesDepartment of Pathology, School of Medicine, Shiraz University of Medical SciencesDepartment of Pathology, School of Medicine, Shiraz University of Medical SciencesDepartment of Biostatistics, Trauma Research Center, School of Medicine, Shiraz University of Medical SciencesShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical SciencesAbstract Background The significance of total and specific subpopulations of tumor-infiltrating lymphocytes (TILs) in cancer is now well-documented. In the present study, we investigated the relevance of CD3+, CD8 +, CD45RO +, and FOXP3 + TILs to the prognosis and survival of patients with bladder cancer and the disease's clinical-pathological parameters. Methods Infiltration of each subset was immunohistochemically evaluated in both stromal and intratumoral regions of tumor tissues from 85 patients with urothelial cell carcinoma of the bladder, with known survival. Results Our results indicated that intratumoral CD45RO+ lymphocytes were significantly higher in high-grade tumors than in low-grade ones (P = 0.028). The frequencies of intratumoral CD3+ (P = 0.002), CD8 + (P = 0.008), intratumoral (P = 0.002), and stromal (P = 0.017) CD45RO+ lymphocytes were also higher in patients with muscular invasion than those without invasion. The frequencies of intratumoral CD3+ (P = 0.043), CD8+ (P = 0.003), CD45RO+ (P = 0.023), and total CD45RO+ (P = 0.015), showed variation in patients with different T-stage, as well; mostly increased in T2 versus Ta and T1. Comparing patients in different stages revealed an increase in the frequencies of total CD3+ (P = 0.011), intratumoral CD3+ (P = 0.006), total CD8+ (P = 0.012), intratumoral CD8+ (P = 0.009) and stromal CD8+ (P = 0.034), as well as total and stromal CD45RO+ lymphocytes (P = 0.01 and P = 0.034, respectively) in stage II comparing to stage I, while the frequencies of stromal CD3+ (P = 0.077) and CD8+ (P = 0.053) cells tended to be decreased in stage III compared to stage II. Conclusions We collectively observed that the frequency of immune cells, especially CD45RO+, CD3+, and CD8+ lymphocytes, were significantly higher in early-progressed tumors. This observation could be explained by continuous and prolonged stimulation of immune cells with tumor antigens during tumor progression or an increase in the recruiting factors, especially in the early stages, to eliminate tumor cells. However, with tumor progression to the late stages, the inhibitory microenvironment provided by tumor cells suppresses or changes the functionality of the effector and memory immune cells to help tumor growth. However, more functional studies with larger sample sizes are needed to reveal the real status of the immune system in patients with bladder cancer.https://doi.org/10.1186/s12894-022-01085-6Bladder cancerTILsCD3CD8CD45ROFOXP3
spellingShingle Ali Ariafar
Alireza Sanati
Simin Ahmadvand
Golsa Shekarkhar
Akbar Safaei
Zahra Shayan
Zahra Faghih
Prognostic significance of immunoscore related markers in bladder cancer
BMC Urology
Bladder cancer
TILs
CD3
CD8
CD45RO
FOXP3
title Prognostic significance of immunoscore related markers in bladder cancer
title_full Prognostic significance of immunoscore related markers in bladder cancer
title_fullStr Prognostic significance of immunoscore related markers in bladder cancer
title_full_unstemmed Prognostic significance of immunoscore related markers in bladder cancer
title_short Prognostic significance of immunoscore related markers in bladder cancer
title_sort prognostic significance of immunoscore related markers in bladder cancer
topic Bladder cancer
TILs
CD3
CD8
CD45RO
FOXP3
url https://doi.org/10.1186/s12894-022-01085-6
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