Harnessing γδ T Cells against Human Gynecologic Cancers.
Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are nearly universally observed in human gynecologic malignancies, correlating with improved outcomes. These cells do not have a clear counterpart in mice but are also found in the healthy female reproductive tract. Interventions that modulate their in vivo activity, or cellular therapies utilizing γδ T cells as an allogeneic, "off-the-shelf" platform (e.g., for chimeric antigen receptor expression) hold significant potential against challenging tumors like ovarian cancer, which has been stubbornly resistant to the immune checkpoint inhibitors that change the landscape of other human tumors. Here, we discuss recent discoveries on the specific populations of γδ T cells that infiltrate human gynecologic cancers, their anti-tumor activity, and the prospect of redirecting their effector function against tumor cells to develop a new generation of immunotherapies that extends beyond the traditional αβ T cell-centric view of the field.
Duke Scholars
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- 4601 Applied computing
- 3104 Evolutionary biology
- 3101 Biochemistry and cell biology
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- 4601 Applied computing
- 3104 Evolutionary biology
- 3101 Biochemistry and cell biology