PD-L1 expression in nonclear-cell renal cell carcinoma

Choueiri, Toni K.; Fay, André P.; Gray, Kathryn P.; Callea, Marcella; Ho, Thai H.; Albigès, Laurence; Bellmunt, Joaquim; Song, Jiuzhou; Carvo, Ingrid; Lampron, Megan E.; Stanton, Melissa L.; Hodi, F. Stephen; McDermott, David F.; Atkins, Michael B.; Freeman, Gordon J.; Hirsch, Michelle S.; Signoretti, Sabina

doi:10.1093/annonc/mdu445

Cited by 268 publications

(189 citation statements)

References 28 publications

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“…This has already been reported in several cancers, 15,58,[62][63][64][65][66] although a favorable prognostic value has been reported in other cancers. 50,55,59,[67][68][69] For comparison and to our knowledge, only four studies-three publications 8,15,42 and one meeting presentation 70 -have described PDL1 expression and clinicopathological correlations in STS.…”

Section: Discussionmentioning

confidence: 64%

PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas

et al. 2017

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Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery. PDL1 expression was heterogeneous across the samples. PDL1-high samples (41%) were more frequently leiomyosarcomas and liposarcomas, and showed more frequently a complex genetic profile and a high-risk CINSARC signature. No correlation existed with other clinicopathological features such as tumor site, depth, and pathological tumor grade and size. In multivariate prognostic analysis, the PDL1-high class was associated with shorter MFS, independently of the pathological type and the CINSARC signature. Analysis of correlations with biological factors suggested the existence in tumors of the PDL1-high class of a strong and efficient cytotoxic T-cell response, however associated with some degree of T-cell exhaustion and negative regulation. In conclusion, we show that PDL1 expression refines the prediction of metastatic relapse in operated localized STS, and that PD1/PDL1 blockade holds potential to improve patient survival by reactivating inhibited T cells to increase the antitumor immune in PDL1-high tumors.

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Section: Discussionmentioning

confidence: 64%

PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas

et al. 2017

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“…The percentages of tumor cells with positive PD-L1 staining were quantified. In accordance with previous studies, PD-L1 tumor positivity was defined as membrane staining of ≥5% tumor cells 18,23,29 .…”

Section: Methodsmentioning

confidence: 67%

“…So far, only one study has attempted to measure PD-L1 expression in Xp11.2 RCCs. Choueiri et al reported that out of 10 Xp11.2 RCC patients, 3 had positive PD-L1 expression in tumor cells and 9 harbored PD-L1-positive tumor infiltrating immune cells 23 . However, the prognostic value of these findings and their correlation with clinical variables were not analyzed due to limited patient numbers.…”

mentioning

confidence: 99%

PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness

Qu¹,

Chang²,

Dai³

et al. 2017

European Urology Supplements

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Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). Renal cell carcinoma (RCC) is widely recognized as a heterogeneous disease with various histological subtypes. The most common histopathological subtypes are clear cell (60%-75%), papillary (10%-15%), chromophobe (5%), and collecting duct carcinomas 1 . Xp11.2 translocation RCC (Xp11.2 RCC) is a rare subtype that was recognized as a distinctive pathological entity in the 2004 World Health Organization renal tumor classification 2, 3 . Xp11.2 RCC is characterized by several translocations on chromosome Xp11.2, resulting in gene fusion between TFE3 and at least six possible partners [4][5][6] .As it is a rare RCC subtype, the best treatment for Xp11.2 RCC has not been defined. Surgery is the optimal treatment for localized Xp11.2 RCC patients, including those with positive regional lymph nodes 7 . However, previous studies indicate that Xp11.2 RCC presents at an advanced stage with a rapid clinical course 8,9 . As a result, systematic treatment may be indispensable for most patients. Anti-VEGF drugs are reported to have activity against metastatic Xp11.2 RCC 10, 11 . However, Xp11.2 RCC has poor prognosis regardless of treatment 12,13 . Therefore, new, effective treatments are desperately needed for patients with this tumor type.Monoclonal antibodies (mAbs) targeting the programmed death 1 (PD1)/programmed death ligand-1 (PD-L1) pathway have achieved impressive response rates in patients with melanoma, non-small cell lung cancer, and bladder cancer, and PD-L1 has been validated as a predictive biomarker for the outcome of mAb therapy in many studies [14][15][16] . However, its prognostic and clinical value in patients with Xp11.2 RCC subtypes is unknown. In this study, we sought to investigate the levels of PD-L1 expression and its correlation with clinical outcome in a series of patients with Xp11.2 RCC that was histologically confirmed using TFE3 break-apart fluorescence in situ hybridization (FISH).

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“…Current and future research will evaluate checkpoint inhibition in neoadjuvant and adjuvant settings, as first-line therapy, and in combination therapy regimens for advanced disease. The use of checkpoint inhibition in pRCC is a promising area of investigation as 10% of pRCC tumors have been shown to express programmed deathligand 1 (PD-L1) a rate similar to the expression in clear cell RCC tumors (27,28).…”

Section: Future Directionsmentioning

confidence: 99%

Improving our understanding of papillary renal cell carcinoma with integrative genomic analysis

Modi

Singer

2016

Ann. Transl. Med.

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Papillary renal cell carcinoma (pRCC) is a heterogeneous and incompletely understood histologic subtype of kidney cancer. Recently, authors from The Cancer Genome Atlas Research Network performed a comprehensive molecular characterization of pRCC. Using multiple analytic methods, they identified 4 subgroups of pRCC with varied genotypic anomalies and probabilities of overall survival. This analysis elucidated the differences between type 1 and type 2 pRCC. Furthermore, type 2 pRCC was found to be heterogeneous itself, with at least 3 subtypes with distinct molecular features. This improved characterization and insight about potential driver mutations and altered pathways may lead to the development of more targeted agents and better patient stratification in clinical trials for pRCC.

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PD-L1 expression in nonclear-cell renal cell carcinoma

Cited by 268 publications

References 28 publications

PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas

PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas

PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness

Improving our understanding of papillary renal cell carcinoma with integrative genomic analysis

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