Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites

Harriet M. Kluger, Christopher R. Zito, Meaghan L. Barr, Marina K. Baine, Veronica L S Chiang, Mario Sznol, David L. Rimm, Lieping Chen, Lucia B. Jilaveanu

Research output: Contribution to journalArticle

Abstract

Purpose: Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas. Experimental Design: We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence. Results: High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01). Conclusions: T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites.

Original languageEnglish (US)
Pages (from-to)3052-3060
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number13
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

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Melanoma
Ligands
T-Lymphocytes
Neoplasm Metastasis
Tumor-Infiltrating Lymphocytes
Neoplasms
Brain
T-Lymphocyte Subsets
Fluorescent Antibody Technique
Research Design
Skin
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kluger, H. M., Zito, C. R., Barr, M. L., Baine, M. K., Chiang, V. L. S., Sznol, M., ... Jilaveanu, L. B. (2015). Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clinical Cancer Research, 21(13), 3052-3060. https://doi.org/10.1158/1078-0432.CCR-14-3073

Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. / Kluger, Harriet M.; Zito, Christopher R.; Barr, Meaghan L.; Baine, Marina K.; Chiang, Veronica L S; Sznol, Mario; Rimm, David L.; Chen, Lieping; Jilaveanu, Lucia B.

In: Clinical Cancer Research, Vol. 21, No. 13, 01.07.2015, p. 3052-3060.

Research output: Contribution to journalArticle

Kluger, HM, Zito, CR, Barr, ML, Baine, MK, Chiang, VLS, Sznol, M, Rimm, DL, Chen, L & Jilaveanu, LB 2015, 'Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites', Clinical Cancer Research, vol. 21, no. 13, pp. 3052-3060. https://doi.org/10.1158/1078-0432.CCR-14-3073
Kluger, Harriet M. ; Zito, Christopher R. ; Barr, Meaghan L. ; Baine, Marina K. ; Chiang, Veronica L S ; Sznol, Mario ; Rimm, David L. ; Chen, Lieping ; Jilaveanu, Lucia B. / Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 13. pp. 3052-3060.
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T1 - Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites

AU - Kluger, Harriet M.

AU - Zito, Christopher R.

AU - Barr, Meaghan L.

AU - Baine, Marina K.

AU - Chiang, Veronica L S

AU - Sznol, Mario

AU - Rimm, David L.

AU - Chen, Lieping

AU - Jilaveanu, Lucia B.

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N2 - Purpose: Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas. Experimental Design: We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence. Results: High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01). Conclusions: T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites.

AB - Purpose: Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas. Experimental Design: We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence. Results: High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01). Conclusions: T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites.

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