Abstract The CD27-CD70 pathway regulates T-cell activity either positively or negatively depending on the context of immune response. Typically, CD27 is known as a co-stimulatory receptor expressed on T cells while CD70 is the ligand expressed on antigen-presenting cells. Interestingly, CD70 is also expressed on T cells upon activation, raising an intriguing question about whether potential CD27-CD70 interaction within T cells affects T-cell response. To address this question in an antigen-specific adoptive T-cell model for tumor immunotherapy, we bred Pmel transgenic mice (JAX strain: 005023) with Cd70-/- mice to generate Pmel-Cd70-/- mice. We found that both CD27 and CD70 are expressed on Pmel T cells activated by GP100 antigen in vivo. Interestingly, T cells expressed CD27 protein at higher frequencies and higher levels in Pmel-Cd70-/- mice compared to Pmel mice with intact Cd70 gene, indicating CD27-CD70 reciprocal regulation. We inoculated Cd27-/-Cd70-/- mice with B16-F10 melanoma cells, then adoptively transferred Pmel versus Pmel-Cd70-/- T cells to compare their efficacy in controlling tumor growth. This unique system eliminates CD27-CD70–mediated interaction between host cells and adoptive T cells, allowing us to distinguish the impact of potential CD27-CD70 interaction within adoptive T cells. Our results showed that Pmel and Pmel-Cd70-/- T cells exhibited significant yet equivalent efficacy in inhibiting tumor growth, indicating that potential CD27-CD70 interaction within adoptive T cells does not affect T-cell immunotherapy in this tumor model. This work is informative for designing adoptive T-cell therapy for cancer treatment.
Puppala et al. (Thu,) studied this question.