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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BMC
2022-08-01
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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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