In:
Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. 2 ( 2021-02), p. e001823-
Abstract:
Chemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4 + T cells (T FH ) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by T FH have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8 + T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13 + CD8 + T cells in clear cell renal cell carcinoma (ccRCC). Methods We analyzed prognostic value and immune contexture that associated with CXCL13 + CD8 + T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13 + CD8 + T cells and total CD8 + T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC. Results Intratumoral CXCL13 + CD8 + T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13 + CD8 + T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8 + T cells in high-level CXCL13 + CD8 + T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13 + CD8 + T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3 + regulatory T cells, TLS and decreased natural killer cells, GZMB + cells. Conclusions Intratumoral CXCL13 + CD8 + T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13 + CD8 + T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13 + CD8 + T cells abundance impaired total CD8 + T cells’ immune function. Intratumoral CXCL13 + CD8 + T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13 + CD8 + T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.
Type of Medium:
Online Resource
ISSN:
2051-1426
DOI:
10.1136/jitc-2020-001823
Language:
English
Publisher:
BMJ
Publication Date:
2021
detail.hit.zdb_id:
2719863-7
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