| First Author | Kurtulus S | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 1 | Pages | 181-194.e6 |
| PubMed ID | 30635236 | Mgi Jnum | J:278617 |
| Mgi Id | MGI:6359371 | Doi | 10.1016/j.immuni.2018.11.014 |
| Citation | Kurtulus S, et al. (2019) Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1(-)CD8(+) Tumor-Infiltrating T Cells. Immunity 50(1):181-194.e6 |
| abstractText | An improved understanding of the anti-tumor CD8(+) T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8(+) tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8(+) TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1(-) TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8(+) T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7/Tcf1 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8(+) T cell responses upon immunotherapy. |
