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PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma

Martin de la Fuente, Laura LU ; Westbom-Fremer, Sofia LU orcid ; Arildsen, Nicolai Skovbjerg LU ; Hartman, Linda LU ; Malander, Susanne LU orcid ; Kannisto, Päivi LU ; Måsbäck, Anna LU and Hedenfalk, Ingrid LU orcid (2020) In Virchows Archiv: an international journal of pathology 477(1). p.83-91
Abstract

The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with... (More)

The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P = 0.03, P = 0.007, and P = 0.02, respectively). In the external data set (203 women), high expression of CD274 (encoding PD-L1) was associated with improved OS (P = 0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P = 0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Virchows Archiv: an international journal of pathology
volume
477
issue
1
pages
9 pages
publisher
Springer
external identifiers
  • pmid:31980961
  • scopus:85078323648
ISSN
1432-2307
DOI
10.1007/s00428-020-02751-6
project
Ovarian carcinoma, early detection and prognostication
language
English
LU publication?
yes
id
6142840d-d706-453d-bf88-ad44e0e573b6
date added to LUP
2020-01-27 07:29:15
date last changed
2024-06-12 07:41:08
@article{6142840d-d706-453d-bf88-ad44e0e573b6,
  abstract     = {{<p>The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P = 0.03, P = 0.007, and P = 0.02, respectively). In the external data set (203 women), high expression of CD274 (encoding PD-L1) was associated with improved OS (P = 0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P = 0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.</p>}},
  author       = {{Martin de la Fuente, Laura and Westbom-Fremer, Sofia and Arildsen, Nicolai Skovbjerg and Hartman, Linda and Malander, Susanne and Kannisto, Päivi and Måsbäck, Anna and Hedenfalk, Ingrid}},
  issn         = {{1432-2307}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{83--91}},
  publisher    = {{Springer}},
  series       = {{Virchows Archiv:  an international journal of pathology}},
  title        = {{PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma}},
  url          = {{http://dx.doi.org/10.1007/s00428-020-02751-6}},
  doi          = {{10.1007/s00428-020-02751-6}},
  volume       = {{477}},
  year         = {{2020}},
}