Abstract
Ovarian cancer has the worst prognosis among gynecological cancers. Thus, new ovarian cancer treatment strategies are needed. Currently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibody are attracting attention worldwide. The Food and Drug Administration approved the use of the PD-1 antibody pembrolizumab for solid cancers with microsatellite instability (MSI)-H or mismatch repair (MMR) deficiency in 2017. However, few studies on ovarian carcinoma have evaluated the relationship among MSI status, lymphocyte infiltration into the tumor, and the expression of immune checkpoint molecules by histologic type. We evaluated the expression of MMR proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunohistochemistry in 136 ovarian cancer patients (76, 13, 23, and 24 cases were high-grade serous, mucinous, endometrioid, and clear cell carcinoma, respectively) to investigate the effectiveness of immune checkpoint inhibitors. Only six cases (4.4%) had loss of MMR protein expression. There was no significant relationship between MSI status and age (p = 0.496), FIGO stage (p = 0.357), initial treatment (primary debulking surgery [PDS] or neoadjuvant chemotherapy) (p = 0.419), residual tumor after PDS or interval debulking surgery (p = 0.202), and expression of CD8 (p = 0.126), PD-L1 (p = 0.432), and PD-1 (p = 0.653). These results suggest that only a small number of MSI cases in ovarian cancer can be effectively treated with immune checkpoint inhibitor monotherapy. Therefore, to improve the prognosis of ovarian carcinoma, a combination therapy of immune checkpoint inhibitors and other anticancer drugs is necessary.
Highlights
Surgery, chemotherapy, and radiation therapy have been the mainstays of cancer treatments
We previously reported that microsatellite instability (MSI) could be a biomarker for immune checkpoint inhibitors in endometrial cancer
The presence of tumor-infiltrating lymphocytes (CD8+) and programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1)/programmed cell death-1 (PD-1) expression were significantly higher in the MSI group than in the microsatellite stable (MSS) group in endometrial cancer [29]
Summary
Chemotherapy, and radiation therapy have been the mainstays of cancer treatments. Immune cells recognize and attack cancer cells to suppress their growth. The anti-tumor immune response mediated by cytotoxic T lymphocytes (CTLs) is suppressed when PD-1 expressed on CTLs binds to PD-L1 expressed on cancer cells. Immune checkpoint inhibitors that inhibit the PD-1/PD-L1 pathway have been clinically applied in various cancer types. The response rate of anti-PD-1 antibody was 20–30% in various cancer types; immune checkpoint inhibitors had serious adverse effects [3,4]. The Food and Drug Administration approved the use of the anti-PD-1 antibody pembrolizumab for solid cancers with microsatellite instability (MSI)-H or mismatch repair (MMR) deficiency in May 2017 [5]. Immune checkpoint inhibitors are considered to be effective in solid cancers with MSI-H and MMR deficiency [6,7]
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