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Lynch syndrome-associated epithelial ovarian cancer and its immunological profile

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Rasmussen, Maria ; Lim, Kevin ; Rambech, Eva ; Andersen, Mads Hald ; Svane, Inge Marie ; Andersen, Ove ; Jensen, Lars Henrik ; Nilbert, Mef ; Therkildsen, Christina. / Lynch syndrome-associated epithelial ovarian cancer and its immunological profile. I: Gynecologic Oncology. 2021 ; Bind 162, Nr. 3. s. 686-693.

Bibtex

@article{5f1ae80ca35c43bc9fd53998cc46e38d,
title = "Lynch syndrome-associated epithelial ovarian cancer and its immunological profile",
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, 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.",
keywords = "Hereditary colorectal cancer, HLA class I, Immunoediting, MHC class I",
author = "Maria Rasmussen and Kevin Lim and Eva Rambech and Andersen, {Mads Hald} and Svane, {Inge Marie} and Ove Andersen and Jensen, {Lars Henrik} and Mef Nilbert and Christina Therkildsen",
note = "Copyright {\textcopyright} 2021 Elsevier Inc. All rights reserved.",
year = "2021",
month = sep,
day = "1",
doi = "10.1016/j.ygyno.2021.07.001",
language = "English",
volume = "162",
pages = "686--693",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press",
number = "3",

}

RIS

TY - JOUR

T1 - Lynch syndrome-associated epithelial ovarian cancer and its immunological profile

AU - Rasmussen, Maria

AU - Lim, Kevin

AU - Rambech, Eva

AU - Andersen, Mads Hald

AU - Svane, Inge Marie

AU - Andersen, Ove

AU - Jensen, Lars Henrik

AU - Nilbert, Mef

AU - Therkildsen, Christina

N1 - Copyright © 2021 Elsevier Inc. All rights reserved.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - 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.

AB - 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.

KW - Hereditary colorectal cancer

KW - HLA class I

KW - Immunoediting

KW - MHC class I

UR - http://www.scopus.com/inward/record.url?scp=85110348845&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2021.07.001

DO - 10.1016/j.ygyno.2021.07.001

M3 - Journal article

C2 - 34275654

VL - 162

SP - 686

EP - 693

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 3

ER -

ID: 66871454