Prognostic significance of PD-1 and PD-L1 positive tumor-infiltrating immune cells in ovarian carcinoma

Buderath, Paul; Mairinger, Fabian; Mairinger, Elena; Böhm, Katharina; Mach, Paweł; Schmid, Kurt Werner; Kasimir‐Bauer, Sabine; Bànkfalvi, Àgnes; Westerwick, Daniela; Hager, Thomas

doi:10.1136/ijgc-2019-000609

Cited by 20 publications

(18 citation statements)

References 29 publications

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“…Furthermore, the prognostic significance of PD-L1 in EOC is debatable. Several studies have reported that high levels of PD-1 or PD-L1 are indicators of favorable prognosis [ 51 , 52 , 53 , 54 ]. Specifically, Webb et al found PD-L1 to be associated with higher levels of tumor infiltrating lymphocytes (TILs).…”

Section: Challenges To Pd-1 Therapymentioning

confidence: 99%

The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer

James

Woodman

DiSilvestro

et al. 2020

Cancers

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with an overall 5-year survival of only 47%. As the development of novel targeted therapies is drastically necessary in order to improve patient survival, current EOC clinical trials have heavily focused on immunotherapeutic approaches, centered upon programmed cell death 1 (PD-1) inhibitors. While PD-1 monotherapies have only exhibited modest responses for patients, it has been theorized that in order to enhance EOC patient response to immunotherapy, combinatorial regimens must be investigated. In this review, unique challenges to EOC PD-1 response will be discussed, along with a comprehensive description of both preclinical and clinical studies evaluating PD-1-based combinatorial therapies. Promising aspects of PD-1-based combinatorial approaches are highlighted, while also discussing specific preclinical and clinical areas of research that need to be addressed, in order to optimize EOC patient immunotherapy response.

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Section: Challenges To Pd-1 Therapymentioning

confidence: 99%

The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer

James

Woodman

DiSilvestro

et al. 2020

Cancers

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“…These immune cells can subsequently have a tumor cell action. 9 It has recently been suggested that the presence of intratumoral inflammatory infiltration associated with PD-L1 expression influences survival in HGSC 10,11 with clinical trials using anti-PD-L1 immunotherapy such as pembrolizumab and avelumab showing promising results. 6,[12][13][14][15] Two recent meta-analysis suggested that PD-L1 expression was not linked to tumor histology, overall survival (OS), and progressionfree survival (PFS), but that PD-L1 mRNA expression was closely correlated with poor PFS.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

et al. 2021

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Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones – QR1 and E1L3N – with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.

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“…Another interesting result of our study is the association of PD-L1 expression on chondrosarcoma cells in primary tumors with shorter time to metastatic spreading. Caution has to be exercised in interpreting this finding because the number of tumor samples analysed is small, however in other cancers PD-L1 expression has been associated with metastatic disease (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

High TIL, HLA, and Immune Checkpoint Expression in Conventional High-Grade and Dedifferentiated Chondrosarcoma and Poor Clinical Course of the Disease

et al. 2021

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PurposeThe aim of this study was to characterize chondrosarcoma tumor infiltration by immune cells and the expression of immunologically relevant molecules. This information may contribute to our understanding of the role of immunological events in the pathogenesis of chondrosarcoma and to the rational design of immunotherapeutic strategies.Patients and MethodsA tissue microarray (TMA) containing 52 conventional and 24 dedifferentiated chondrosarcoma specimens was analyzed by immunohistochemical staining for the expression of parameters associated with tumor antigen-specific immune responses, namely, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) and the expression of HLA class I heavy chain, beta-2 microglobulin (β2m), HLA class II and immune checkpoint molecules, B7-H3 and PD-1/PD-L1. The results were correlated with histopathological characteristics and the clinical course of the disease.ResultsCD8+ TILs were present in 21% of the conventional and 90% of the dedifferentiated chondrosarcoma tumors tested. B7-H3 was expressed in 69% of the conventional and 96% of the dedifferentiated chondrosarcoma tumors tested. PD-1 and PD-L1 were expressed 53% and 33% respectively of the dedifferentiated tumors tested. PD-L1 expression was associated with shorter time to metastasis.ConclusionThe tumor infiltration by lymphocytes suggests that chondrosarcoma is immunogenic. Defects in HLA class I antigen and expression of the checkpoint molecules B7-H3 and PD-1/PD-L1 suggest that tumor cells utilize escape mechanisms to avoid immune recognition and destruction. This data implies that chondrosarcoma will benefit from strategies that enhance the immunogenicity of tumor antigens and/or counteract the escape mechanisms.

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Prognostic significance of PD-1 and PD-L1 positive tumor-infiltrating immune cells in ovarian carcinoma

Cited by 20 publications

References 29 publications

The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer

The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

High TIL, HLA, and Immune Checkpoint Expression in Conventional High-Grade and Dedifferentiated Chondrosarcoma and Poor Clinical Course of the Disease

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