Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma.
Br J Cancer
; 126(2): 219-227, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34616011
ABSTRACT
BACKGROUND:
Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients.METHODS:
Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated.RESULTS:
CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors.CONCLUSION:
Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocytes, Tumor-Infiltrating
/
Cellular Senescence
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Cholangiocarcinoma
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Caveolin 1
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Forkhead Transcription Factors
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B7-H1 Antigen
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Cancer-Associated Fibroblasts
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
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Female
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Humans
/
Male
Language:
En
Journal:
Br J Cancer
Year:
2022
Document type:
Article