Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells

Oncotarget
Veethika PandeyDeborah A Altomare

Abstract

Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which m...Continue Reading

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Citations

May 18, 2017·International Journal of Molecular Sciences·Rodrigo Fernandes da SilvaFernando Guimarães
Nov 1, 2018·Oncoimmunology·Jeremiah L OyerAlicja J Copik
Feb 23, 2019·International Journal of Molecular Sciences·Marco GreppiEmanuela Marcenaro
Jun 13, 2020·International Journal of Molecular Sciences·Daria S ChulpanovaValeriya V Solovyeva
Jun 12, 2021·Journal for Immunotherapy of Cancer·Giulia PellizzariSophia N Karagiannis

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Methods Mentioned

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flow cytometry
xenograft

Clinical Trials Mentioned

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Software Mentioned

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