Methylseleninic Acid Sensitizes Ovarian Cancer Cells to T-Cell Mediated Killing by Decreasing PDL1 and VEGF Levels

Nair, Deepika; Rådestad, Emelie; Khalkar, Prajakta; Díaz-Argelich, Nuria; Schroder, Axel; Klynning, Charlotte; Ungerstedt, Johanna; Uhlin, Michael; Fernandes, Aristi P.

doi:10.3389/fonc.2018.00407

Cited by 19 publications

(14 citation statements)

References 41 publications

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“…In addition, Se increases the expression levels of MHC-I antigens on cancer cells in vitro, thus, improving their detection and destruction by CD8 þ T-lymphocytes [61] (Table 2). Furthermore, an in vitro study showed that methylseleninic acid-enhanced T cell-mediated killing of ovarian cancer cells via PD-L1 and VEGF inhibition [62].…”

Section: Lymphocytesmentioning

confidence: 99%

Selenium stimulates the antitumour immunity: Insights to future research

Razaghi¹,

Poorebrahim²,

Sarhan³

et al. 2021

European Journal of Cancer

125

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Selenium is an essential trace element for regulating immune functions through redox-regulating activity of selenoproteins (e.g. glutathione peroxidase), protecting immune cells from oxidative stress. However, in cancer, selenium has biological bimodal action depending on the concentration. At nutritional low doses, selenium, depending on its form, may act as an antioxidant, protecting against oxidative stress, supporting cell survival and growth, thus, plays a chemo-preventive role; while, at supra-nutritional higher pharmacological doses, selenium acts as pro-oxidant inducing redox signalling and cell death. To date, many studies have been conducted on the benefits of selenium intake in reducing the risk of cancer incidence at the nutritional level, indicating that likely selenium functions as an immunostimulator, i.e. reversing the immunosuppression in tumour microenvironment towards antitumour immunity by activating immune cells (e.g. M 1 macrophages and CD8 þ T-lymphocytes) and releasing pro-inflammatory cytokines such as interferon-gamma; whereas, fewer studies have explored the effects of supra-nutritional or pharmacological doses of selenium in cancer immunity. This review, thus, systematically analyses the current knowledge about how selenium stimulates the immune system against cancer and lay the groundwork for future research. Such knowledge can be promising to design combinatorial therapies with Seleniumbased compounds and other modalities like immunotherapy to lower the adverse effects and increase the efficacy of treatments.

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Section: Lymphocytesmentioning

confidence: 99%

Selenium stimulates the antitumour immunity: Insights to future research

Razaghi¹,

Poorebrahim²,

Sarhan³

et al. 2021

European Journal of Cancer

125

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show abstract

“… 5 , 6 Several studies have focused on inflammatory infiltrate, T cells and tumor-associated macrophage (TAM) expression on both OC cell lines and in vivo . 7 PD1 is implicated in programmed cell death and PD1/ PD-L1 is an important immune checkpoint in proliferation and development tumor. 8 Tumor cells with PD-L1 transmembrane protein bind to the PD-1 receptor of T lymphocytes and inactivate them.…”

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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“…Chen et al stated that selenium can decrease EGFR expression in tumor cells and cancer metastasis [ 51 ]. Nair et al reported that methylselenic acid and selenite can decrease PD-L1 and VEGF expressions in cancer cells [ 52 ]. Given lung cancer cells which are resistant to EGFR tyrosine kinase inhibitors, Liao et al discovered that the combination of selenium and n-3 PUFA was able to reverse the acquired resistance in cancer cells [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Positive Effects of Preventive Nutrition Supplement on Anticancer Radiotherapy in Lung Cancer Bearing Mice

Liu

Chiu

et al. 2020

Cancers

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(1) Background: Radiotherapy (RT) is one of the major treatments for non-small cell lung cancer, but RT-associated toxicities usually impede its anticancer effect. Nutrient supplementation has been applied for cancer prevention or a complementary measure to anticancer therapy. Here, we explored the influence of total nutrition supplementation before and after cancer occurrence on the anticancer benefit and side effects of RT. (2) Methods: C57BL/6JNarl mice were inoculated with Lewis lung carcinoma cells and then treated with radiotherapy. TNuF, a total nutrition formula, was prescribed by oral gavage. In the preventive groups, TNuF supplementation started from seven days before tumor inoculation. In the complementary groups, TNuF supplementation began after tumor inoculation. (3) Results: TNuF successfully enhanced the anticancer effect of RT against primary tumor and lung metastasis. Additionally, the complementary supplement improved the high serum TNF-α level and the wasting of sartorius muscle in mice receiving RT. In histologic and molecular analysis, TNuF was observed to modulate EGFR, apoptosis, and VEGF and PD-1/PD-L1 pathways. Furthermore, the anticancer benefit of the preventive supplement was comparable to that of the complementary administration. (4) Conclusions: Our results demonstrated that the prescription of the TNuF total nutrition formula before and after cancer diagnosis attains similar benefits in testing subjects with typical anticancer RT. TNuF is also a potential sensitizer to anti-PD-1 immune therapy.

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Methylseleninic Acid Sensitizes Ovarian Cancer Cells to T-Cell Mediated Killing by Decreasing PDL1 and VEGF Levels

Cited by 19 publications

References 41 publications

Selenium stimulates the antitumour immunity: Insights to future research

Selenium stimulates the antitumour immunity: Insights to future research

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

Positive Effects of Preventive Nutrition Supplement on Anticancer Radiotherapy in Lung Cancer Bearing Mice

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