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Context-dependent roles for autophagy in myeloid cells in tumor progression. | LitMetric

AI Article Synopsis

  • Autophagy has a dual role in cancer: it prevents tumors by removing stress in normal cells but can also aid tumor growth by helping cancer cells cope with stress.
  • Research showed that blocking autophagy specifically in myeloid cells influenced tumor growth in different ways, with mixed outcomes based on the tumor environment.
  • The findings suggest that using broad autophagy inhibitors for cancer treatment may not be effective for all patients, indicating the need for more tailored approaches in therapy.

Article Abstract

Autophagy is known to suppress tumor initiation by removing genotoxic stresses in normal cells. Conversely, autophagy is also known to support tumor progression by alleviating metabolic stresses in neoplastic cells. Centered on this pro-tumor role of autophagy, there have been many clinical trials to treat cancers through systemic blocking of autophagy. Such systemic inhibition affects both tumor cells and non-tumor cells, and the consequence of blocked autophagy in non-tumor cells in the context of tumor microenvironment is relatively understudied. Here, we examined the effect of autophagy-deficient myeloid cells on the progression of autophagy-competent tumors. We found that blocking autophagy only in myeloid cells modulated tumor progression markedly but such effects were context dependent. In a tumor implantation model, the growth of implanted tumor cells was substantially reduced in mice with autophagy-deficient myeloid cells; T cells infiltrated deeper into the tumors and were responsible for the reduced growth of the implanted tumor cells. In an oncogene-driven tumor induction model, however, tumors grew faster and metastasized more in mice with autophagy-deficient myeloid cells. These data demonstrate that the autophagy status of myeloid cells plays a critical role in tumor progression, promoting or suppressing tumor growth depending on the context of tumor-myeloid cell interactions. This study indicates that systemic use of autophagy inhibitors in cancer therapy may have differential effects on rates of tumor progression in patients due to effects on myeloid cells and that this warrants more targeted use of selective autophagy inhibitors in a cancer therapy in a clinical setting.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275940PMC
http://dx.doi.org/10.1101/2024.07.12.603292DOI Listing

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