Lynch syndrome-associated epithelial ovarian cancer and its immunological profile
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Lynch syndrome-associated epithelial ovarian cancer and its immunological profile. / Rasmussen, Maria; Lim, Kevin; Rambech, Eva; Andersen, Mads Hald; Svane, Inge Marie; Andersen, Ove; Jensen, Lars Henrik; Nilbert, Mef; Therkildsen, Christina.
I: Gynecologic Oncology, Bind 162, Nr. 3, 2021, s. 686-693.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
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 - Corrigendum: https://www.sciencedirect.com/science/article/pii/S0090825821016012?via%3Dihub
PY - 2021
Y1 - 2021
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
U2 - 10.1016/j.ygyno.2021.07.001
DO - 10.1016/j.ygyno.2021.07.001
M3 - Journal article
C2 - 34275654
AN - SCOPUS:85110348845
VL - 162
SP - 686
EP - 693
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 3
ER -
ID: 302067871