Abstract
Despite their role in cancer surveillance, adoptive immunotherapy using γδ T-cells has
achieved limited efficacy. To enhance trafficking to bone marrow, circulating Vγ9Vδ2 T cells are expanded in serum-free medium containing TGF-β1 and IL-2 (γδ[T2] cells) or
medium containing IL-2 alone (γδ[2] cells, as the control). Unexpectedly, the yield and
viability of γδ[T2] cells are also increased by TGF-β1, when compared to γδ[2]
controls. γδ[T2] cells are less differentiated and yet display increased cytolytic activity,
cytokine release and anti-tumor activity in several leukemic and solid tumor
models. Efficacy is further enhanced by cancer cell sensitization using
aminobisphosphonates or Ara-C. A number of contributory effects of TGF-β were
identified, including prostaglandin E 2 receptor downmodulation, TGF-β insensitivity
and upregulated integrin activity. Biological relevance is supported by the identification of a favorable γδ[T2] signature in acute myeloid leukemia (AML). Given their enhanced therapeutic activity and compatibility with allogeneic use, γδ[T2] cells warrant evaluation in cancer immunotherapy.
achieved limited efficacy. To enhance trafficking to bone marrow, circulating Vγ9Vδ2 T cells are expanded in serum-free medium containing TGF-β1 and IL-2 (γδ[T2] cells) or
medium containing IL-2 alone (γδ[2] cells, as the control). Unexpectedly, the yield and
viability of γδ[T2] cells are also increased by TGF-β1, when compared to γδ[2]
controls. γδ[T2] cells are less differentiated and yet display increased cytolytic activity,
cytokine release and anti-tumor activity in several leukemic and solid tumor
models. Efficacy is further enhanced by cancer cell sensitization using
aminobisphosphonates or Ara-C. A number of contributory effects of TGF-β were
identified, including prostaglandin E 2 receptor downmodulation, TGF-β insensitivity
and upregulated integrin activity. Biological relevance is supported by the identification of a favorable γδ[T2] signature in acute myeloid leukemia (AML). Given their enhanced therapeutic activity and compatibility with allogeneic use, γδ[T2] cells warrant evaluation in cancer immunotherapy.
| Original language | English |
|---|---|
| Journal | Cell Reports Medicine |
| Publication status | Accepted/In press - 18 Nov 2021 |
Keywords
- Gamma delta T-cell,
- TGF-b,
- acute myeloid leukemia,
- prostaglandin E2,
- aminobisphosphonate,
- Ara-C
