Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer

Maureen L. Drakes; Swati Mehrotra; Monica Aldulescu; Ronald K. Potkul; Yueying Liu; Anne Grisoli; Cara Joyce; Timothy O'Brien; M. Sharon Stack; Patrick J. Stiff

doi:10.1186/s13048-018-0414-z

Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer

Maureen L. Drakes, Swati Mehrotra, Monica Aldulescu, Ronald K. Potkul, Yueying Liu, Anne Grisoli, Cara Joyce, Timothy O'Brien, M. Sharon Stack, Patrick J. Stiff

Loyola University Chicago

Research output: Contribution to journal › Article › peer-review

Abstract

<p> <h3> Background </h3> <p id="x-x-Par1"> Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. <p id="x-x-Par2"> We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. <h3> Results </h3> <p id="x-x-Par3"> Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease ( <em> P </em>  = 0.028 and <em> P </em>  = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) ( <em> P </em>  = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. <h3> Conclusions </h3> <p id="x-x-Par4"> We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling. </p> </p> </p> </p></p>

Original language	American English
Journal	Mathematics and Statistics: Faculty Publications and Other Works
Volume	11
Issue number	43
DOIs	https://doi.org/10.1186/s13048-018-0414-z
State	Published - May 30 2018

Keywords

Programmed cell death-1
Programmed cell death-1 ligand
High grade disease
Cancer immunotherapy
Ovarian cancer

Disciplines

Mathematics
Obstetrics and Gynecology
Oncology

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Drakes, M. L., Mehrotra, S., Aldulescu, M., Potkul, R. K., Liu, Y., Grisoli, A., Joyce, C., O'Brien, T., Stack, M. S., & Stiff, P. J. (2018). Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer. Mathematics and Statistics: Faculty Publications and Other Works, 11(43). https://doi.org/10.1186/s13048-018-0414-z

Drakes, ML, Mehrotra, S, Aldulescu, M, Potkul, RK, Liu, Y, Grisoli, A, Joyce, C, O'Brien, T, Stack, MS & Stiff, PJ 2018, 'Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer', Mathematics and Statistics: Faculty Publications and Other Works, vol. 11, no. 43. https://doi.org/10.1186/s13048-018-0414-z

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title = "Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer",

abstract = " Background Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. Results Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease ( P  = 0.028 and P  = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) ( P  = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. Conclusions We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling. ",

keywords = "Programmed cell death-1, Programmed cell death-1 ligand, High grade disease, Cancer immunotherapy, Ovarian cancer",

author = "Drakes, {Maureen L.} and Swati Mehrotra and Monica Aldulescu and Potkul, {Ronald K.} and Yueying Liu and Anne Grisoli and Cara Joyce and Timothy O'Brien and Stack, {M. Sharon} and Stiff, {Patrick J.}",

year = "2018",

month = may,

day = "30",

doi = "10.1186/s13048-018-0414-z",

language = "American English",

volume = "11",

journal = "Mathematics and Statistics: Faculty Publications and Other Works",

number = "43",

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TY - JOUR

T1 - Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer

AU - Drakes, Maureen L.

AU - Mehrotra, Swati

AU - Aldulescu, Monica

AU - Potkul, Ronald K.

AU - Liu, Yueying

AU - Grisoli, Anne

AU - Joyce, Cara

AU - O'Brien, Timothy

AU - Stack, M. Sharon

AU - Stiff, Patrick J.

PY - 2018/5/30

Y1 - 2018/5/30

N2 - Background Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. Results Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease ( P  = 0.028 and P  = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) ( P  = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. Conclusions We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling.

AB - Background Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. Results Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease ( P  = 0.028 and P  = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) ( P  = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. Conclusions We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling.

KW - Programmed cell death-1

KW - Programmed cell death-1 ligand

KW - High grade disease

KW - Cancer immunotherapy

KW - Ovarian cancer

UR - https://ecommons.luc.edu/math_facpubs/22

U2 - 10.1186/s13048-018-0414-z

DO - 10.1186/s13048-018-0414-z

M3 - Article

VL - 11

JO - Mathematics and Statistics: Faculty Publications and Other Works

JF - Mathematics and Statistics: Faculty Publications and Other Works

IS - 43

ER -

Stratification of Ovarian Tumor Pathology by Expression of Programmed Cell Death-1 (PD-1) and PD-ligand- 1 (PD-L1) in Ovarian Cancer

Abstract

Keywords

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