Immunotherapy of Ovarian Cancer with Particular Emphasis on the PD-1/PDL-1 as Target Points

Świderska, Janina; Kozłowski, Mateusz; Kwiatkowski, Sebastian; Cymbaluk‐Płoska, Aneta

doi:10.3390/cancers13236063

Cited by 10 publications

(18 citation statements)

References 71 publications

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“…The first immunological drug used in ovarian cancer was bevacizumab (a recombinant humanized monoclonal antibody blocking angiogenesis by inhibiting VEGF-A (vascular endothelial growth factor A). Immune drugs with a different mechanism of action include immune checkpoint inhibitors [ 8 ]. Immune checkpoint inhibitors are not only used to treat ovarian cancer but also other malignancies, such as kidney and lung cancer [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer

et al. 2022

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It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic lesions. Three proteins involved in the immune response were studied: PD-1, PD-L1, and CTLA-4. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CTLA-4 was 0.595 pg/mL, with the sensitivity and specificity of 70.3% and 90.7% (p = 0.000004). Unfavorable prognostic factors determined in serum were: PD-L1 (for PFS: HR 1.18, 95% CI 1.11–1.21, p = 0.016; for OS: HR 1.17, 95% CI 1.14–1.19, p = 0.048) and PD-1 (for PFS: HR 1.01, 95% CI 0.91–1.06, p = 0.035). Unfavorable prognostic factors determined in peritoneal fluid were: PD-L1 (for PFS: HR 1.08, 95% CI 1.01–1.11, p = 0.049; for OS: HR 1.14, 95% CI 1.10–1.17, p = 0.045) and PD-1 (for PFS: HR 1.21, 95% CI 1.19–1.26, p = 0.044). We conclude that CTLA-4 should be considered as a potential biomarker in the diagnosis of ovarian cancer. PD-L1 and PD-1 concentrations are unfavorable prognostic factors for ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer

et al. 2022

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“…Interactions in the tumor microenvironment (TME) appear to be the promising targets in up-and-coming OC treatment [ 16 , 17 , 18 , 19 , 20 , 21 ]. The immune system cells in TME are exposed to many signals that determine their immunophenotype and can manipulate their functions [ 22 ].…”

Section: Ovarian Cancer—a Global Problemmentioning

confidence: 99%

The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients

Pawłowska

Skiba

Suszczyk

et al. 2022

Cancers

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The prognosis for ovarian cancer (OC) patients is poor and the five-year survival rate is only 47%. Immune checkpoints (ICPs) appear to be the potential targets in up-and-coming OC treatment. However, the response of OC patients to immunotherapy based on programmed cell death pathway (PD-1/PD-L1) inhibitors totals only 6–15%. The promising approach is a combined therapy, including other ICPs such as the T-cell immunoglobulin and ITIM domain/CD155/DNAX accessory molecule-1 (TIGIT/CD155/DNAM-1) axis. Preclinical studies in a murine model of colorectal cancer showed that the dual blockade of PD-1/PD-L1 and TIGIT led to remission in the whole studied group vs. the regression of the tumors with the blockade of a single pathway. The approach stimulates the effector activity of T cells and NK cells, and redirects the immune system activity against the tumor. The understanding of the synergistic action of the TIGIT and PD-1/PD-L1 blockade is, however, poor. Thus, the aim of this review is to summarize the current knowledge about the mode of action of the dual TIGIT and PD-1/PD-L1 blockade and its potential benefits for OC patients. Considering the positive impact of this combined therapy in malignancies, including lung and colorectal cancer, it appears to be a promising approach in OC treatment.

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“…Furthermore, carboplatin plus paclitaxel chemotherapy, beyond killing tumor cells, has been also shown to reduce immunosuppression for 2 weeks coinciding with an enhanced T cell immunity, by potentially creating a window of opportunity to identify the optimal time to introduce an ICI-based therapy [ 120 , 135 , 136 , 137 ]. In particular, ICIs targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) or PD-L1/PD-1 are among the most innovative molecules in this field [ 138 ]. Anti-CTLA-4 antibodies improve naive T cell priming and activation in lymph nodes, where they eventually move to promote tumor rejection.…”

Section: Predictive Role Of Tils In Ovarian Cancermentioning

confidence: 99%

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

Fanale

Dimino

Pedone

et al. 2022

Cancers

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In the last decade, tumor-infiltrating lymphocytes (TILs) have been recognized as clinically relevant prognostic markers for improved survival, providing the immunological basis for the development of new therapeutic strategies and showing a significant prognostic and predictive role in several malignancies, including ovarian cancer (OC). In fact, many OCs show TILs whose typology and degree of infiltration have been shown to be strongly correlated with prognosis and survival. The OC histological subtype with the higher presence of TILs is the high-grade serous carcinoma (HGSC) followed by the endometrioid subtype, whereas mucinous and clear cell OCs seem to contain a lower percentage of TILs. The abundant presence of TILs in OC suggests an immunogenic potential for this tumor. Despite the high immunogenic potential, OC has been described as a highly immunosuppressive tumor with a high expression of PD1 by TILs. Although further studies are needed to better define their role in prognostic stratification and the therapeutic implication, intraepithelial TILs represent a relevant prognostic factor to take into account in OC. In this review, we will discuss the promising role of TILs as markers which are able to reflect the anticancer immune response, describing their potential capability to predict prognosis and therapy response in OC.

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Immunotherapy of Ovarian Cancer with Particular Emphasis on the PD-1/PDL-1 as Target Points

Cited by 10 publications

References 71 publications

Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer

Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer

The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

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