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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
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.
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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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