Lynch syndrome-associated epithelial ovarian cancer and its immunological profile
(2021) In Gynecologic Oncology 162(3). p.686-693- Abstract
Introduction: Lynch syndrome is a multi-tumor syndrome characterized by mismatch repair deficiency (MMR-d), microsatellite instability (MSI), and increased tumor-infiltrating lymphocytes (TILs) making these tumors candidates for treatment with immune checkpoint inhibitors. However, response may depend on tumor-induced immune evasion mechanisms, e.g. loss of Beta-2-Microglobulin (B2M) or upregulation of programmed death protein ligand 1 (PD-L1). We investigated the immune response and B2M and PD-L1 expression in Lynch syndrome-associated ovarian cancers. Methods: We successfully analyzed 30 Lynch syndrome-associated epithelial ovarian cancers collected through the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) register. MMR-d,... (More)
Introduction: Lynch syndrome is a multi-tumor syndrome characterized by mismatch repair deficiency (MMR-d), microsatellite instability (MSI), and increased tumor-infiltrating lymphocytes (TILs) making these tumors candidates for treatment with immune checkpoint inhibitors. However, response may depend on tumor-induced immune evasion mechanisms, e.g. loss of Beta-2-Microglobulin (B2M) or upregulation of programmed death protein ligand 1 (PD-L1). We investigated the immune response and B2M and PD-L1 expression in Lynch syndrome-associated ovarian cancers. Methods: We successfully analyzed 30 Lynch syndrome-associated epithelial ovarian cancers collected through the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) register. MMR-d, MSI, immune response (CD3, CD8, and CD68), and immune evasion mechanisms (B2M and PD-L1) were investigated. Statistical associations between these markers were evaluated in addition to survival in relation to B2M/PD-L1. Results: Of the 29 evaluable tumors, 27 were MMR-d (93.1%). Likewise of 26 evaluable tumors, 14 were MSI (53.8%). MMR-d/MMR-proficiency associated with MSI/MSS in 60.0%. Half of the ovarian tumors presented with high levels of TILs. Loss of B2M expression was observed in 46.7% of the tumors, while expression of PD-L1 was seen in 28.0% of the cases. There was no association between B2M/PD-L1 and MSI/TILs/survival. Loss of B2M was often seen in tumors with low TILs (p = 0.056 or p = 0.059 for CD3 and CD8 positive cells, respectively). Conclusion: MMR-d, MSI, and TILs are also seen in Lynch syndrome-associated ovarian cancers making these potential candidates for checkpoint-based immunotherapy. The clinical impact from immune evasion through loss of B2M needs to be investigated further in larger cohorts.
(Less)
- author
- Rasmussen, Maria ; Lim, Kevin ; Rambech, Eva LU ; Andersen, Mads Hald ; Svane, Inge Marie ; Andersen, Ove ; Jensen, Lars Henrik ; Nilbert, Mef LU and Therkildsen, Christina LU
- organization
- publishing date
- 2021-09-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Hereditary colorectal cancer, HLA class I, Immunoediting, MHC class I
- in
- Gynecologic Oncology
- volume
- 162
- issue
- 3
- pages
- 8 pages
- publisher
- Academic Press
- external identifiers
-
- pmid:34275654
- scopus:85110348845
- ISSN
- 0090-8258
- DOI
- 10.1016/j.ygyno.2021.07.001
- language
- English
- LU publication?
- yes
- id
- 0f73b661-0c6e-419a-ac17-bc86527c32fd
- date added to LUP
- 2021-09-07 14:05:27
- date last changed
- 2024-04-06 08:26:38
@article{0f73b661-0c6e-419a-ac17-bc86527c32fd,
abstract = {{<p>Introduction: Lynch syndrome is a multi-tumor syndrome characterized by mismatch repair deficiency (MMR-d), microsatellite instability (MSI), and increased tumor-infiltrating lymphocytes (TILs) making these tumors candidates for treatment with immune checkpoint inhibitors. However, response may depend on tumor-induced immune evasion mechanisms, e.g. loss of Beta-2-Microglobulin (B2M) or upregulation of programmed death protein ligand 1 (PD-L1). We investigated the immune response and B2M and PD-L1 expression in Lynch syndrome-associated ovarian cancers. Methods: We successfully analyzed 30 Lynch syndrome-associated epithelial ovarian cancers collected through the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) register. MMR-d, MSI, immune response (CD3, CD8, and CD68), and immune evasion mechanisms (B2M and PD-L1) were investigated. Statistical associations between these markers were evaluated in addition to survival in relation to B2M/PD-L1. Results: Of the 29 evaluable tumors, 27 were MMR-d (93.1%). Likewise of 26 evaluable tumors, 14 were MSI (53.8%). MMR-d/MMR-proficiency associated with MSI/MSS in 60.0%. Half of the ovarian tumors presented with high levels of TILs. Loss of B2M expression was observed in 46.7% of the tumors, while expression of PD-L1 was seen in 28.0% of the cases. There was no association between B2M/PD-L1 and MSI/TILs/survival. Loss of B2M was often seen in tumors with low TILs (p = 0.056 or p = 0.059 for CD3 and CD8 positive cells, respectively). Conclusion: MMR-d, MSI, and TILs are also seen in Lynch syndrome-associated ovarian cancers making these potential candidates for checkpoint-based immunotherapy. The clinical impact from immune evasion through loss of B2M needs to be investigated further in larger cohorts.</p>}},
author = {{Rasmussen, Maria and Lim, Kevin and Rambech, Eva and Andersen, Mads Hald and Svane, Inge Marie and Andersen, Ove and Jensen, Lars Henrik and Nilbert, Mef and Therkildsen, Christina}},
issn = {{0090-8258}},
keywords = {{Hereditary colorectal cancer; HLA class I; Immunoediting; MHC class I}},
language = {{eng}},
month = {{09}},
number = {{3}},
pages = {{686--693}},
publisher = {{Academic Press}},
series = {{Gynecologic Oncology}},
title = {{Lynch syndrome-associated epithelial ovarian cancer and its immunological profile}},
url = {{http://dx.doi.org/10.1016/j.ygyno.2021.07.001}},
doi = {{10.1016/j.ygyno.2021.07.001}},
volume = {{162}},
year = {{2021}},
}