Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model
Cancer patients who are overweight compared to those with normal body weight have obesity-associated alterations of natural killer (NK) cells, characterized by poor cytotoxicity, slow proliferation, and inadequate anti-cancer activity. Concomitantly, prohibitin overexpressed by cancer cells elevates...
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MDPI AG
2021-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/8/1279 |
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| author | Seungmin Han Minjin Jung Angela S. Kim Daniel Y. Lee Byung-Hyun Cha Charles W. Putnam Kwang Suk Lim David A. Bull Young-Wook Won |
| author_facet | Seungmin Han Minjin Jung Angela S. Kim Daniel Y. Lee Byung-Hyun Cha Charles W. Putnam Kwang Suk Lim David A. Bull Young-Wook Won |
| author_sort | Seungmin Han |
| collection | DOAJ |
| description | Cancer patients who are overweight compared to those with normal body weight have obesity-associated alterations of natural killer (NK) cells, characterized by poor cytotoxicity, slow proliferation, and inadequate anti-cancer activity. Concomitantly, prohibitin overexpressed by cancer cells elevates glucose metabolism, rendering the tumor microenvironment (TME) more tumor-favorable, and leading to malfunction of immune cells present in the TME. These changes cause vicious cycles of tumor growth. Adoptive immunotherapy has emerged as a promising option for cancer patients; however, obesity-related alterations in the TME allow the tumor to bypass immune surveillance and to down-regulate the activity of adoptively transferred NK cells. We hypothesized that inhibiting the prohibitin signaling pathway in an obese model would reduce glucose metabolism of cancer cells, thereby changing the TME to a pro-immune microenvironment and restoring the cytolytic activity of NK cells. Priming tumor cells with an inhibitory the prohibitin-binding peptide (PBP) enhances cytokine secretion and augments the cytolytic activity of adoptively transferred NK cells. NK cells harvested from the PBP-primed tumors exhibit multiple markers associated with the effector function of active NK cells. Our findings suggest that PBP has the potential as an adjuvant to enhance the cytolytic activity of adoptively transferred NK cells in cancer patients with obesity. |
| first_indexed | 2024-03-10T08:28:06Z |
| format | Article |
| id | doaj.art-324329cacd0147d89a475316c5a68eaf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T08:28:06Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-324329cacd0147d89a475316c5a68eaf2023-11-22T09:15:24ZengMDPI AGPharmaceutics1999-49232021-08-01138127910.3390/pharmaceutics13081279Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer ModelSeungmin Han0Minjin Jung1Angela S. Kim2Daniel Y. Lee3Byung-Hyun Cha4Charles W. Putnam5Kwang Suk Lim6David A. Bull7Young-Wook Won8Division of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USAInterdisciplinary Program in Biohealth-Machinery Convergence Engineering, Department of Biotechnology and Bioengineering, College of Art, Culture and Engineering, Kangwon National University, Chuncheon 24341, KoreaDivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine—Tucson, Tucson, AZ 85724, USACancer patients who are overweight compared to those with normal body weight have obesity-associated alterations of natural killer (NK) cells, characterized by poor cytotoxicity, slow proliferation, and inadequate anti-cancer activity. Concomitantly, prohibitin overexpressed by cancer cells elevates glucose metabolism, rendering the tumor microenvironment (TME) more tumor-favorable, and leading to malfunction of immune cells present in the TME. These changes cause vicious cycles of tumor growth. Adoptive immunotherapy has emerged as a promising option for cancer patients; however, obesity-related alterations in the TME allow the tumor to bypass immune surveillance and to down-regulate the activity of adoptively transferred NK cells. We hypothesized that inhibiting the prohibitin signaling pathway in an obese model would reduce glucose metabolism of cancer cells, thereby changing the TME to a pro-immune microenvironment and restoring the cytolytic activity of NK cells. Priming tumor cells with an inhibitory the prohibitin-binding peptide (PBP) enhances cytokine secretion and augments the cytolytic activity of adoptively transferred NK cells. NK cells harvested from the PBP-primed tumors exhibit multiple markers associated with the effector function of active NK cells. Our findings suggest that PBP has the potential as an adjuvant to enhance the cytolytic activity of adoptively transferred NK cells in cancer patients with obesity.https://www.mdpi.com/1999-4923/13/8/1279prohibitin binding peptideNK cellimmunotherapyobesitytumor microenvironment |
| spellingShingle | Seungmin Han Minjin Jung Angela S. Kim Daniel Y. Lee Byung-Hyun Cha Charles W. Putnam Kwang Suk Lim David A. Bull Young-Wook Won Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model Pharmaceutics prohibitin binding peptide NK cell immunotherapy obesity tumor microenvironment |
| title | Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model |
| title_full | Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model |
| title_fullStr | Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model |
| title_full_unstemmed | Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model |
| title_short | Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model |
| title_sort | peptide adjuvant to invigorate cytolytic activity of nk cells in an obese mouse cancer model |
| topic | prohibitin binding peptide NK cell immunotherapy obesity tumor microenvironment |
| url | https://www.mdpi.com/1999-4923/13/8/1279 |
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