| Autor: |
Thacker, Gatha, Henry, Samantha, Nandi, Ajeya, Debnath, Rahul, Singh, Snahlata, Nayak, Anupma, Susnik, Barbara, Boone, Melinda M, Zhang, Qing, Kesmodel, Susan B, Gumber, Sanjeev, Das, Gokul M, Kambayashi, Taku, Dos Santos, Camila O., Chakrabarti, Rumela |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 3/8/2023, Vol. 15 Issue 686, p1-15, 15p |
| Abstrakt: |
Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3highCD11b−CD27− immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell–mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti–programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC. Immature NK cells aid cancer: Natural Killer (NK) cells are generally thought to be an effective contributor to antitumor immune responses. However, not all NK cells are created equal. Here, Thacker et al. demonstrated that Socs3highCD11b–CD27– immature NK cells were present in samples from patients with triple negative breast cancer (TNBC) and correlated with worse prognosis. The authors further showed that this population of NK cells promoted, rather than inhibited, tumor progression in mice. Depletion of this population of NK cells or inhibition of Wnt ligand secretion prevented this effect, suggesting that these immature NK cells may represent a therapeutic target for TNBC. —CM [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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