Dataset Information

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer.

ABSTRACT:

Background

PD-L1 expression predicts response to immune checkpoint inhibitors in renal cell carcinomas (RCC), but has also been suggested to be linked to poor patient outcome.

Methods

We analyzed PD-L1 in > 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8⁺ cytotoxic cells.

Result

At a cut-off level of 5% PD-L1 positive tumor cells, PD-L1 positivity was seen in 6.3% of 633 clear cell RCC (ccRCC), 18.2% of 165 papillary RCC, 18.8% of 64 chromophobe RCC, and 41.7% of 103 oncocytomas. In ccRCC, PD-L1 positivity was significantly linked to high ISUP (p < 0.0001), Fuhrman (p < 0.0001), Thoenes grade (p < 0.0001), distant metastasis (p = 0.0042), short recurrence-free (p < 0.0001), and overall survival (p = 0.0002). Intratumoral CD8⁺ lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; p < 0.0001). PD-L positive immune cells were seen in 8.2% of all RCC and 13.9% of papillary RCC. In ccRCC, PD-L1 positive immune cells were linked to high numbers of tumor-infiltrating CD8⁺ cells (p < 0.0001), high ISUP (p < 0.0001), Fuhrman (p = 0.0027), and Thoenes grade (p < 0.0001), and poor tumor-specific survival (p = 0.0280).

Conclusions

These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.

SUBMITTER: Moller K

PROVIDER: S-EPMC8599390 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.