The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures
- Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW & University Medical Centre Utrecht, Netherlands
- Oncode Institute, Hubrecht Institute-KNAW, Netherlands
- Roche Pharma Research and early Development, Switzerland
Figures
Figure 1
Dynamic crosstalk between pro- and antitumorigenic macrophage subtypes and tumor cells.
(A) Macrophage differentiation is highly heterogenous and depends mostly on the environmental cues within their niche. The classical binary division includes the M1 (tumoricidal and pro-inflammatory) and M2 (tumor-supporting and antiinflammatory) polarization. The increasingly favored macrophage division considers macrophage diversity as a spectrum and includes tumor-associated macrophages (TAMs), alveolar macrophages (AMs), and interstitial macrophages (IMs) as separate subtypes with mostly pro-tumor properties in LC/NSCLC. The dynamic macrophage-tumor crosstalk within the TME results in different activation of the immune cells and confers a range of effects that can either aid the tumor development and progression or halt it. The included differentiation factors are the most represented within the existing literature. A range of other cues were found to contribute to macrophage differentiation but their effect is not yet well defined. The red and orange boxes mark all the macrophage subtypes that are generally considered pro-tumorigenic in LC/NSCLC settings and their associated effects on tumor cells (and vice versa). IL, interleukin; GM-CSF, granulocyte macrophage colony-stimulating factor; TGF, transforming growth factor; GCs, glucocorticoids; IFN, interferon; LPS, lipopolysaccharides. (B) The prognosis and survival of NSCLC patients are reflected by the macrophage infiltrate within the tumor islets. Greater M1 infiltrate generally indicates a favorable prognosis, while the predominance of M2 predicts reduced survival.
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Figure 2
The reductionist and the holistic approaches to generate cancer organoids.
In the reductionist approach, healthy lung epithelial cells are genetically engineered to carry non-small cell lung cancer (NSCLC) driver mutations. This approach works best if the cell of origin is known and culture conditions have already been established, to generate isogenic organoid lines. In the holistic approach, tumor-derived cancer cells are isolated and propagated as tumor organoids. If a healthy biopsy of the same patient can be obtained, this approach leads to matched patient organoids.
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Figure 3
Two organoid co-culture approaches incorporating immune components of the tumor microenvironment (TME).
In the intrinsic TME approach the non-epithelial cells of the TME are conserved along with the tumor cells. In the reconstituted TME approach tumor cells are isolated from the initial tumor biopsy and cultured separately from the immune cells. Immune cells sourced from peripheral blood or from the same tissue sample can then be added to the co-culture to reconstitute the TME in a controlled manner. Several methods can be used for immune cell-tumor organoid co-cultures: submerged organoid culture, micro-fluidic devices (organ-on-a-chip), or transwell cultures.
Created with BioRender.com.
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The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures
eLife 12:e82998.
https://doi.org/10.7554/eLife.82998
