Expression of multiple immune checkpoint molecules on Tï¿½cells in malignant ascites from epithelial ovarian carcinoma

Imai, Yumiko; Matsushita, Hirokazu; Fujieda, Nao; Sato, Shigeo; Miyagi, Etsuko; Kakimi, Kazuhiro

doi:10.3892/ol.2018.8101

Cited by 41 publications

(47 citation statements)

References 37 publications

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“…Twenty-seven cytokines, including interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL15, IL-17, bFGF, Eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF in sera were measured using Bio-Plex Pro human Cytokine 27-plex Assay (Bio-Rad Laboratories, Inc., Hercules, CA, USA) 35 . Full details are described in Imai et al 35 . Briefly, sera were incubated with microbeads labeled with specific antibodies to one of the aforementioned cytokines for 60 min.…”

Section: Methodsmentioning

confidence: 99%

Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

Yabuno

Matsushita

Hamano

et al. 2020

Sci Rep

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Serum cytokine and chemokine networks may reflect the complex systemic immunological interactions in cancer patients. Studying groups of cytokines and their networks may help to understand their clinical biology. A total of 178 cases of ovarian cancer were analyzed in this study, including 73 high-grade serous (HGSC), 66 clear cell (CCC) and 39 endometrioid carcinomas. Suspension cytokine arrays were performed with the patients’ sera taken before the primary surgery. Associations between each cytokine and clinicopathological factors were analyzed in all patients using multivariate linear regression models, and cluster analyses were performed for each histotype. In the multivariate analyses, twelve of 27 cytokines were correlated with histotypes. Cluster analyses in each histotype revealed 2 cytokine signatures S1 and S2 in HGSC, and similarly C1 and C2 in CCC. Twenty-two of 27 cytokines were commonly clustered in HGSC and CCC. Signature S1 and C1 included IL-2,6,8,15, chemokines and angiogenic factors, whereas signature S2 and C2 included IL-4,5,9,10,13, TNF-α and G-CSF. Four subgroups based on a high or low level for each signature were identified, and this cluster-based classification demonstrated significantly different progression-free and overall survivals for CCC patients (P = 0.00097 and P = 0.017).

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Section: Methodsmentioning

confidence: 99%

Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

Yabuno

Matsushita

Hamano

et al. 2020

Sci Rep

Self Cite

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“…Other trials that are still ongoing focus on different lymphocyte surface molecule inhibitors such as TIM-3 and LAG-3, or agonists of co-stimulatory proteins that can prove their effectiveness in the future [13,14].…”

Section: Szkolenie Podyplomowementioning

confidence: 99%

“…Trwają badania nad inhibitorami innych cząsteczek obecnych na powierzchni limfocytów m.in. TIM-3 i LAG-3, jak również nad agonistami białek kostymulujących, które w przyszłości mogą znaleźć zastosowanie w immunoterapii nowotworów [13,14].…”

Section: Funding Sources: Noneunclassified

Endocrine complications of cancer immunotherapy

Król

Gawlik

Jarząb

2018

Endokrynologia Polska

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Immunotherapy using monoclonal antibodies -checkpoint inhibitors -is a dynamically evolving discipline of clinical oncology and a new hope for patients with advanced and disseminated cancer. However, the activation of T-lymphocytes can at the same time lead to autoimmune response and destruction of healthy organs, which is a serious adverse effect that can also affect the endocrine system. Here we present possible endocrine complications of immunotherapy with contemporary inhibitors of immune checkpoints (CTLA-4, PD-1, PD-L1/L2), their frequency, symptoms, and proposed grade-dependent treatment. Failure to diagnose endocrine pathology can in adverse circumstances lead to treatment failure and condemn the patient's fate. Due to tremendous progress in cancer immunotherapy during the last few years and an increase in the number of treated patients, endocrinologists should become acquainted with the specificity of this mode of oncological treatment. (Endokrynol Pol 2018; 69 (6): 722-733)  Endocrine complications of immunotherapy Aleksandra Król et al.

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“…However, clinical responses can vary significantly between patients and reflect the heterogeneous nature of individual tumors and their microenvironment (TME) (4,6,7). Ovarian cancer is known to respond poorly to immune checkpoint blockade (ICB) with clinical trials reporting responses ranging from 6%-22% (8,9). Clearly, there is a knowledge gap between our current understanding of immune regulation and how it can be manipulated to enhance the clinical efficacy of ICB therapies in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the low response to ICB therapy, high-grade serous ovarian cancer was one of the first human cancers to have demonstrated a relationship between increased tumor-infiltrating lymphocytes (TILs) and increased patient survival (8,13). A major challenge remains to boost the clinical efficacy of ICB in ovarian cancer and overcome low mutational burden and an immunosuppressive tumor microenvironment comprised of regulatory T cells, macrophages and PD-1 signaling (14) .…”

Section: Introductionmentioning

confidence: 99%

Neutralizing PD-L1 and PD-L2 Enhances the Efficacy of Immune Checkpoint Inhibitors in Ovarian Cancer

Miao

Thakkar

Qian

et al. 2020

Preprint

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One Sentence Summary: Dual Inhibition of PD-L1 and PD-L2 using an affinity enhanced sPD-1 decoy molecule delivers superior antitumor activity when compared with αPD-1 and αPD-L1 antibodies in ovarian cancer. Abstract:Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have improved for a number of solid tumors. Unfortunately, ovarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB) with reported low patient response rates. Using IHC staining, we find that PD-L2 is highly expressed in ovarian cancers and other malignancies with sub-optimal response to ICB, and is expressed at low levels in cancers responsive to ICB. Based on this observation, we hypothesized that the elevated expression of PD-L2 produced by both tumor and surrounding stromal cells contributes to immune-suppression. Since PD-L2 has been reported to have a 6-to10-fold higher native binding affinity to PD-1 compared with PD-L1, we hypothesized that high levels of PD-L2 can lead to insufficient blockade of the PD-1 signaling pathway. To overcome the immune repressive activity of PD-L2, we engineered a soluble PD-1 decoy molecule (sPD-1 mutant) that binds and neutralizes both PD-L1 and PD-L2 with a 10,000-and 200-fold improvement in binding affinity, respectively, when compared to wild-type binding to these same molecules. Such enhancement in binding affinity is facilitated by amino acid mutations both within and outside of the binding interface. Furthermore, this high affinity sPD-1 mutant molecule demonstrates superior in vivo efficacy in multiple cancer models including ovarian cancer where PD-L2 is highly expressed on the cell surface.

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Expression of multiple immune checkpoint molecules on Tï¿½cells in malignant ascites from epithelial ovarian carcinoma

Cited by 41 publications

References 37 publications

Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

Endocrine complications of cancer immunotherapy

Neutralizing PD-L1 and PD-L2 Enhances the Efficacy of Immune Checkpoint Inhibitors in Ovarian Cancer

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