Jisup Kim1, Sinae Kim2, Hye Sun Lee2, Wookyeom Yang3, Hanbyoul Cho3, Doo Byung Chay3, Seong Jin Cho4, Soonwon Hong1, Jae-Hoon Kim5. 1. Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Department of Pathology, Hallym University Kangdong Sacred Heart Hospital, 150 Seongan-ro, Gangdong-gu, Seoul, Republic of Korea. 5. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: jaehoonkim@yuhs.ac.
Abstract
OBJECTIVE: Monoclonal antibodies targeting programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) demonstrated promising clinical response. The predictive/prognostic value of PD-1/PD-L1 immunohistochemistry (IHC) has been evaluated in many cancer types. However, the prognostic value of PD-1/PD-L1 IHC has not been evaluated in endometrial cancer. METHODS: We conducted a retrospective study to quantify the IHC CD8, PD-1, and PD-L1 expressions in immune cells at center of tumor (CT), invasive margin (IM), and/or tumor cell in 183 primary endometrial cancer samples from a single cohort, followed by their reciprocal combinations, including compartmental differences, and correlated them with overall survival (OS) and progression-free survival (PFS). RESULTS: In repeated Cox multivariable models adjusted by clinicoimmunopathologic factors, high CT-PD-L1 was an independent adverse prognostic factor for PFS in all patients and in the microsatellite-stable subgroup. Immune marker ratios revealed independently shorter PFS for high CT-PD-L1/CT-CD8 and CT-PD-L1/CT-PD-1 ratios. Classification of endometrial cancer into four groups based on CT-CD8 and CT-PD-L1 revealed significantly different survival among groups. CONCLUSIONS: The high PD-L1/CD8 ratio and the high expression of PD-L1 on immune cells were independent poor prognostic factors for PFS in endometrial cancer, providing insights into the tumor microenvironment.
OBJECTIVE: Monoclonal antibodies targeting programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) demonstrated promising clinical response. The predictive/prognostic value of PD-1/PD-L1 immunohistochemistry (IHC) has been evaluated in many cancer types. However, the prognostic value of PD-1/PD-L1 IHC has not been evaluated in endometrial cancer. METHODS: We conducted a retrospective study to quantify the IHC CD8, PD-1, and PD-L1 expressions in immune cells at center of tumor (CT), invasive margin (IM), and/or tumor cell in 183 primary endometrial cancer samples from a single cohort, followed by their reciprocal combinations, including compartmental differences, and correlated them with overall survival (OS) and progression-free survival (PFS). RESULTS: In repeated Cox multivariable models adjusted by clinicoimmunopathologic factors, high CT-PD-L1 was an independent adverse prognostic factor for PFS in all patients and in the microsatellite-stable subgroup. Immune marker ratios revealed independently shorter PFS for high CT-PD-L1/CT-CD8 and CT-PD-L1/CT-PD-1 ratios. Classification of endometrial cancer into four groups based on CT-CD8 and CT-PD-L1 revealed significantly different survival among groups. CONCLUSIONS: The high PD-L1/CD8 ratio and the high expression of PD-L1 on immune cells were independent poor prognostic factors for PFS in endometrial cancer, providing insights into the tumor microenvironment.
Authors: Mickey V Patel; Zheng Shen; Marta Rodriguez-Garcia; Edward J Usherwood; Laura J Tafe; Charles R Wira Journal: Front Immunol Date: 2021-04-23 Impact factor: 7.561
Authors: Ramy R Saleh; Jordan L Scott; Nicholas Meti; Danielle Perlon; Rouhi Fazelzad; Alberto Ocana; Eitan Amir Journal: Mol Diagn Ther Date: 2022-02-01 Impact factor: 4.074