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Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade
Treatments aiming to augment immune checkpoint blockade (ICB) in cancer often focus on T cell immunity, but innate immune cells may have important roles to play. Here, we demonstrate a single-dose combination treatment (termed AIP) using a pan-tumor-targeting antibody surrogate, half-life-extended i...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653865/ https://www.ncbi.nlm.nih.gov/pubmed/34818534 http://dx.doi.org/10.1016/j.celrep.2021.110021 |
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author | Wang, Chensu Cui, Ang Bukenya, Maurice Aung, Aereas Pradhan, Dikshant Whittaker, Charles A. Agarwal, Yash Thomas, Ayush Liang, Simon Amlashi, Parastoo Suh, Heikyung Spranger, Stefani Hacohen, Nir Irvine, Darrell J. |
author_facet | Wang, Chensu Cui, Ang Bukenya, Maurice Aung, Aereas Pradhan, Dikshant Whittaker, Charles A. Agarwal, Yash Thomas, Ayush Liang, Simon Amlashi, Parastoo Suh, Heikyung Spranger, Stefani Hacohen, Nir Irvine, Darrell J. |
author_sort | Wang, Chensu |
collection | PubMed |
description | Treatments aiming to augment immune checkpoint blockade (ICB) in cancer often focus on T cell immunity, but innate immune cells may have important roles to play. Here, we demonstrate a single-dose combination treatment (termed AIP) using a pan-tumor-targeting antibody surrogate, half-life-extended interleukin-2 (IL-2), and anti-programmed cell death 1 (PD-1), which primes tumors to respond to subsequent ICB and promotes rejection of large established tumors in mice. Natural killer (NK) cells and macrophages activated by AIP treatment underwent transcriptional reprogramming; rapidly killed cancer cells; governed the recruitment of cross-presenting dendritic cells (DCs) and other leukocytes; and induced normalization of the tumor vasculature, facilitating further immune infiltration. Thus, innate cell-activating therapies can initiate critical steps leading to a self-sustaining cycle of T cell priming driven by ICB. |
format | Online Article Text |
id | pubmed-8653865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-86538652021-12-08 Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade Wang, Chensu Cui, Ang Bukenya, Maurice Aung, Aereas Pradhan, Dikshant Whittaker, Charles A. Agarwal, Yash Thomas, Ayush Liang, Simon Amlashi, Parastoo Suh, Heikyung Spranger, Stefani Hacohen, Nir Irvine, Darrell J. Cell Rep Article Treatments aiming to augment immune checkpoint blockade (ICB) in cancer often focus on T cell immunity, but innate immune cells may have important roles to play. Here, we demonstrate a single-dose combination treatment (termed AIP) using a pan-tumor-targeting antibody surrogate, half-life-extended interleukin-2 (IL-2), and anti-programmed cell death 1 (PD-1), which primes tumors to respond to subsequent ICB and promotes rejection of large established tumors in mice. Natural killer (NK) cells and macrophages activated by AIP treatment underwent transcriptional reprogramming; rapidly killed cancer cells; governed the recruitment of cross-presenting dendritic cells (DCs) and other leukocytes; and induced normalization of the tumor vasculature, facilitating further immune infiltration. Thus, innate cell-activating therapies can initiate critical steps leading to a self-sustaining cycle of T cell priming driven by ICB. 2021-11-23 /pmc/articles/PMC8653865/ /pubmed/34818534 http://dx.doi.org/10.1016/j.celrep.2021.110021 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Wang, Chensu Cui, Ang Bukenya, Maurice Aung, Aereas Pradhan, Dikshant Whittaker, Charles A. Agarwal, Yash Thomas, Ayush Liang, Simon Amlashi, Parastoo Suh, Heikyung Spranger, Stefani Hacohen, Nir Irvine, Darrell J. Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
title | Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
title_full | Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
title_fullStr | Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
title_full_unstemmed | Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
title_short | Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
title_sort | reprogramming nk cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653865/ https://www.ncbi.nlm.nih.gov/pubmed/34818534 http://dx.doi.org/10.1016/j.celrep.2021.110021 |
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