Summary of how the factors in the TME impact CD4+ T cell functions
| TME factor/Cell type . | Impact on CD4+ T cell functions . | References . |
|---|---|---|
| Acidity/lactate | I ↑ Treg differentiation | Comito et al. (2019) |
| ↓ Th1/Th17 effector programs | Comito et al. (2019), Krol et al. (2022) | |
| ↓ TCR signaling via induction of Cbl-b | Bosticardo et al. (2001), Pilon-Thomas et al. (2016), Huber et al. (2017), Tsai et al. (2023) | |
| Hypoxia | ↑ Treg differentiation | Ben-Shoshan et al. (2008), Neildez-Nguyen et al. (2015) |
| ↑ Suppressive IL10+ Th17 CD4s | Volchenkov et al. (2017) | |
| ↓ Th1 effector program via IL10 signaling | Shehade et al. (2015) | |
| ER stress | ↓ Activation and effector functions in CD4+ T cells | Song et al. (2018), Cao et al. (2019) |
| ↓ Th1 polarization | ||
| CAFs | ↓ Effector function in CD4+ T cells | Erez et al. (2010), Fiori et al. (2019), Butti et al. (2021), Chen et al. (2024a) |
| ↑ Suppressive Tregs | Liao et al. (2009), Monte et al. (2011), Huang et al. (2022) | |
| ↑ Th2-CD4+ T cells | Barnas et al. (2010), Kerdidani et al. (2022) | |
| Prime anti-tumor Th1/Th17 CD4+ T cells | ||
| Tumor-associated suppressive myeloid cells | Produce suppressive factors that inhibit Th1 effector programs in CD4+ T cells | Beltra et al. (2020), Xia et al. (2022), Zhou et al. (2024) |
| ↓ Amino acids essential for T cell function | ||
| Prime CD4+ T cells to become anergic/Tregs | ||
| Induce tumor-promoting Th17 CD4+ T cells | ||
| cDC2s, cDC1s, and M1-like macrophages | Prime anti-tumor CD4+ T cells | Ferris et al. (2020), Iwanowycz et al. (2021), Patterson et al. (2023) |
| TME factor/Cell type . | Impact on CD4+ T cell functions . | References . |
|---|---|---|
| Acidity/lactate | I ↑ Treg differentiation | Comito et al. (2019) |
| ↓ Th1/Th17 effector programs | Comito et al. (2019), Krol et al. (2022) | |
| ↓ TCR signaling via induction of Cbl-b | Bosticardo et al. (2001), Pilon-Thomas et al. (2016), Huber et al. (2017), Tsai et al. (2023) | |
| Hypoxia | ↑ Treg differentiation | Ben-Shoshan et al. (2008), Neildez-Nguyen et al. (2015) |
| ↑ Suppressive IL10+ Th17 CD4s | Volchenkov et al. (2017) | |
| ↓ Th1 effector program via IL10 signaling | Shehade et al. (2015) | |
| ER stress | ↓ Activation and effector functions in CD4+ T cells | Song et al. (2018), Cao et al. (2019) |
| ↓ Th1 polarization | ||
| CAFs | ↓ Effector function in CD4+ T cells | Erez et al. (2010), Fiori et al. (2019), Butti et al. (2021), Chen et al. (2024a) |
| ↑ Suppressive Tregs | Liao et al. (2009), Monte et al. (2011), Huang et al. (2022) | |
| ↑ Th2-CD4+ T cells | Barnas et al. (2010), Kerdidani et al. (2022) | |
| Prime anti-tumor Th1/Th17 CD4+ T cells | ||
| Tumor-associated suppressive myeloid cells | Produce suppressive factors that inhibit Th1 effector programs in CD4+ T cells | Beltra et al. (2020), Xia et al. (2022), Zhou et al. (2024) |
| ↓ Amino acids essential for T cell function | ||
| Prime CD4+ T cells to become anergic/Tregs | ||
| Induce tumor-promoting Th17 CD4+ T cells | ||
| cDC2s, cDC1s, and M1-like macrophages | Prime anti-tumor CD4+ T cells | Ferris et al. (2020), Iwanowycz et al. (2021), Patterson et al. (2023) |
cDC2, type-2 conventional DCs; cDC1, type-1 conventional DCs.