Overall survival and PD‐L1 expression in metastasized malignant melanoma

Gadiot, Jules; Hooijkaas, Anna I.; Kaiser, Andrew; Tinteren, Harm van; Boven, Hester van; Blank, C.U.

doi:10.1002/cncr.25747

Cited by 214 publications

(162 citation statements)

References 64 publications

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“…PD-L1 was more expressed in satellite and in-transit metastases compared with lymph node, and distant metastases. In this study, PD-L1 did not correlate with disease free or overall survival [65].…”

Section: Pd-1 Expression In Intratumoral Cd8 Cells: Independent Effeccontrasting

confidence: 73%

See 1 more Smart Citation

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

Merelli

Massi

Cattaneo

et al. 2014

Critical Reviews in Oncology/Hematology

154

108

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Section: Pd-1 Expression In Intratumoral Cd8 Cells: Independent Effeccontrasting

confidence: 73%

“…There are important differences in the first two above referenced studies [47,65]. PD-L1 was evaluated with different immunostaining protocols.…”

Section: Pd-1 Expression In Intratumoral Cd8 Cells: Independent Effecmentioning

confidence: 99%

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

Merelli

Massi

Cattaneo

et al. 2014

Critical Reviews in Oncology/Hematology

154

108

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“…immune cells in the tumor microenvironment were also evaluated. Detection of immunosuppressive markers including PD-L1, CTLA-4, and IDO has been reported for various tumor types [4,[15][16][17][18][19][20][21][22][23][24][25][26][27]. In our study, the positive expression of PD-L1, CTLA-4, and IDO was noted in 43.6, 65.8, and 47.7 % of the cases, respectively.…”

Section: Discussionsupporting

confidence: 59%

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

et al. 2014

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Background There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). Methods In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(?), CD4(?), CD8(?), or PD-1(?) cells] within the tumor microenvironment were measured using immunohistochemical analysis. Results Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/ moderately differentiated adenocarcinoma (P \ 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(?) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (P values \0.05)]. Survival outcomes were also better in patients with a higher density of CD3(?) cells within the tumor microenvironment than in those with a lower density of CD3(?) cells [5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (P values \0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. Conclusions GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(?) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.

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“…This issue has been explained in detail by Gadiot et al in their recent report. 39 Positive staining, in our view, should be membranous, which may or may not be accompanied also by cytoplasmic staining.…”

Section: Discussionmentioning

confidence: 74%

PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome

et al. 2016

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Therapeutic blockade of PD-1/PD-L1 can have dramatic therapeutic benefit in some patients; however, the prognostic associations of PD-1 and its ligands, in the absence of therapeutic blockade have not been definitively addressed. In particular, associations of PD-L2 with immune infiltrates and with outcome have yet to be explored. We hypothesized that surface expression of both PD-L1 and PD-L2 by melanoma cells would be associated with immune cell infiltration and with overall patient survival, independent of checkpoint blockade therapy. We also characterized the heterogeneity of their distribution within a tumor and within tumors of the same patient. Tissue microarrays of metastatic melanoma samples from 147 patients were quantified for CD8 C , CD45, CD4 C , CD3, CD163, CD20, CD138, FoxP3, PD-1, PD-L1 and PD-L2 markers by immunohistochemistry. Relationships between the proportions of PD-L1 and PD-L2 expressing tumor cells with the immune cell count, distribution (immunotype) and patient survival were studied. Expressions of both PD-L1 and PD-L2 correlated significantly with increasing densities of immune cells in the tumor specimens and with immunotype. Positive PD-L2 expression was associated with improved overall survival and the simultaneous positive expression of both PD-1 ligands showed a higher association with survival. Significant heterogeneity of PD-L1 and PD-L2 expressions within tumors were observed, however, they were less pronounced with PD-L2. In conclusion, both are markers of immune infiltration and PD-L2, alone or in combination with PD-L1, is a marker for prognosis in metastatic melanoma patients. Larger tumor samples yield more reliable assessments of PD-L1/L2 expression.

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Overall survival and PD‐L1 expression in metastasized malignant melanoma

Cited by 214 publications

References 64 publications

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome

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