Proinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy

Yanan Xue, Xiaojie Yan, Da Li, Shurong Dong and Yuan Ping ()
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Yanan Xue: School of Medicine, Zhejiang University
Xiaojie Yan: Zhejiang University
Da Li: School of Medicine, Zhejiang University
Shurong Dong: Zhejiang University
Yuan Ping: School of Medicine, Zhejiang University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract The success of macrophage-based adoptive cell therapy is largely constrained by poor polarization from alternatively activated (M2-like) to classically activated (M1-like) phenotype in the immunosuppressive tumor microenvironment (TME). Here, we show that the engineered macrophage (eMac) with a heat-inducible genetic switch can induce both self-polarization of adoptively transferred eMac and re-polarization of tumour-associated macrophages in response to mild temperature elevation in a mouse model. The locoregional production of proinflammatory cytokines by eMac in the TME dose not only induces the strong polarization of macrophages into a classically activated phenotype, but also ensures that the side effects typical for systemically administrate proinflammatory cytokines are avoided. We also present a wearable warming device which is adaptable for human patients and can be remotely controlled by a smartphone. In summary, our work represents a safe and efficient adoptive transfer immunotherapy method with potential for human translation.

Date: 2024
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DOI: 10.1038/s41467-024-46210-1

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