Recurrences of Superficial Bladder Carcinoma are Associated with a Raise of CD8high&gt;CD57+ and CD8low T Lymphocytes in Peripheral Blood

Jacobs, John J. L.; Characiejus, Dainius; Paukonien, Vita; Jankeviius, Feliksas; Moorselaar, R. Jeroen A. van; Mauricas, Mykolas; Otter, W. Den

doi:10.2174/1876401001003010008

Cited by 3 publications

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“…On the other hand, Jacobs et al (29) found a significant increase in the number of peripheral blood CD8+ lymphocytes in patients with recurrent NMIBC. They hypothesized that these peripheral immune suppressive cells facilitated tumor recurrences or that tumor recurrences caused an increase in the peripheral immunosuppressive lymphocytes (29). …”

Section: Discussionmentioning

confidence: 96%

The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes

et al. 2012

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AimTo evaluate whether tumor infiltrating lymphocytes (TIL) in biopsy specimens are associated with the clinical outcome of non-muscle invasive bladder cancer.MethodsWe retrieved tumor specimens from 115 patients with solitary papillary non-muscle invasive bladder cancer treated between 1996 and 2006 and constructed tissue microarrays. Patients were divided in two groups: those with recurrent disease (N = 69) and those without recurrent disease (N = 46) during the follow up of minimum 5 years. All patients were treated with initial transurethral resection and none received adjuvant therapy. Immunhistochemical staining was performed with anti-CD3, CD4, CD8, and Granzyme B (GrB). The CD4+:CD8+ and GrB+:CD8 ratios were determined.ResultsTumor infiltrating lymphocytes were predominantly observed within cancer stroma, and only rare individual cells were observed intraepithelially. The group without recurrent disease had lower levels of CD3+ and CD8+ lymphocytes than the group with recurrent disease (P = 0.0001, P = 0.0002, respectively). The CD4+:GrB+ and GrB+:CD8+ ratios were significantly higher in patients without recurrent disease (P = 0.0002, P = 0.039, respectively).ConclusionThis study revealed a possible connection between TIL number and bladder cancer recurrence. TIL subset ratio showed different patterns in recurrent and non-recurrent tumors, which is why it could become a useful a prognostic clinical index if our findings are confirmed in randomized trials.

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Section: Discussionmentioning

confidence: 96%

The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes

et al. 2012

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CD8highCD57+ T-cell population as an independent predictor of response to chemoradiation therapy in extensive-stage small cell lung cancer

et al. 2015

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Single-cell analysis reveals clonally expanded tumor-associated CD57⁺CD8 T cells are enriched in the periphery of patients with metastatic urothelial cancer responding to PD-L1 blockade

Fehlings¹,

Kim²,

Guan³

et al. 2022

J Immunother Cancer

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BackgroundA growing body of evidence suggests that T-cell responses against neoantigens are critical regulators of response to immune checkpoint blockade. We previously showed that circulating neoantigen-specific CD8 T cells in patients with lung cancer responding to anti-Programmed death-ligand 1 (PD-L1) (atezolizumab) exhibit a unique phenotype with high expression of CD57, CD244, and KLRG1. Here, we extended our analysis on neoantigen-specific CD8 T cells to patients with metastatic urothelial cancer (mUC) and further profiled total CD8 T cells to identify blood-based predictive biomarkers of response to atezolizumab.MethodsWe identified tumor neoantigens from 20 patients with mUC and profiled their peripheral CD8 T cells using highly multiplexed combinatorial tetramer staining. Another set of patients with mUC treated with atezolizumab (n=30) or chemotherapy (n=40) were selected to profile peripheral CD8 T cells by mass cytometry. Using single-cell transcriptional analysis (single-cell RNA sequencing (scRNA-seq)), together with CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and paired T-cell receptor (TCR) sequencing, we further characterized peripheral CD8 T cells in a subset of patients (n=16).ResultsHigh frequency of CD57 was observed in neoantigen-specific CD8 T cells in patients with mUC responding to atezolizumab. Extending these findings to bulk CD8 T cells, we found higher frequency of CD57 expressing CD8 T cells before treatment in patients responding to atezolizumab (n=20, p<0.01) but not to chemotherapy. These findings were corroborated in a validation cohort (n=30, p<0.01) and notably were independent of known biomarkers of response. scRNA-seq analysis identified a clonally expanded cluster enriched within CD57+ CD8 T cells in responding patients characterized by higher expression of genes associated with activation, cytotoxicity, and tissue-resident memory markers. Furthermore, compared with CD57− CD8 T cells, TCRs of CD57+ CD8 T cells showed increased overlap with the TCR repertoire of tumor-infiltrating T cells.ConclusionsCollectively, we show high frequencies of CD57 among neoantigen-specific and bulk CD8 T cells in patients responding to atezolizumab. The TCR repertoire overlap between peripheral CD57+ CD8 T cells and tumor-infiltrating lymphocytes suggest that accumulation of peripheral CD57+ CD8 T cells is reflective of an ongoing antitumor T-cell response. Our findings provide evidence and rationale for using circulating CD8 T cells expressing CD57 as a readily accessible blood-based biomarker for selecting patients with mUC for atezolizumab therapy.

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Recurrences of Superficial Bladder Carcinoma are Associated with a Raise of CD8high>CD57+ and CD8low T Lymphocytes in Peripheral Blood

Cited by 3 publications

References 51 publications

The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes

The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes

CD8highCD57+ T-cell population as an independent predictor of response to chemoradiation therapy in extensive-stage small cell lung cancer

Single-cell analysis reveals clonally expanded tumor-associated CD57⁺CD8 T cells are enriched in the periphery of patients with metastatic urothelial cancer responding to PD-L1 blockade

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Recurrences of Superficial Bladder Carcinoma are Associated with a Raise of CD8high>CD57+ and CD8low T Lymphocytes in Peripheral Blood

Cited by 3 publications

References 51 publications

The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes

The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes

CD8highCD57+ T-cell population as an independent predictor of response to chemoradiation therapy in extensive-stage small cell lung cancer

Single-cell analysis reveals clonally expanded tumor-associated CD57+CD8 T cells are enriched in the periphery of patients with metastatic urothelial cancer responding to PD-L1 blockade

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Single-cell analysis reveals clonally expanded tumor-associated CD57⁺CD8 T cells are enriched in the periphery of patients with metastatic urothelial cancer responding to PD-L1 blockade