[CCoE Notice] Dissertation Announcement: Melisa J. Montalvo, "Understanding Cytotoxic Mechanisms of Cancer Immunotherapies"

[Greenwell, Stephen J]

[Dissertation Defense Announcement at the Cullen College of Engineering]
Understanding Cytotoxic Mechanisms
of Cancer Immunotherapies

Melisa J. Montalvo

April 11, 2025; 9 a.m. to 10:30 a.m.
Location: AERB 222 or Zoom<https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/85258985300__;!!LkSTlj0I!H0_MIUDnocH1ra9dWxidN4rkvhrxA-n5rJ-Ue_dBug6E8URx5B79NVDBTLfKjg_KuDPUBCYUajf7FtN-HFujlSCqCkE$ >

Committee Chair:
Navin Varadarajan, Ph.D.
Committee Members:
Mehmet Orman, Ph.D. | Richard Willson, Ph.D. | Meghana Trivedi, Pharm.D., Ph.D. |
Nabil Ahmed, Ph.D.
Abstract
Immunotherapies have revolutionized our ability to treat cancers effectively; therapeutics like antibody-based therapies have yielded clinical success. Cancer immunotherapies rely on a patients' immune cells to elicit anti-tumor responses; however not all patients respond to these therapeutics. To decode these discrepancies in response and understand the molecular mechanisms associated with these therapeutics, a deep understanding of immune cell cytotoxicity is required to fully understand how to augment their anti-tumor efficacy.

Here, we explore the molecular mechanisms of antibody-dependent cellular cytotoxicity (ADCC) in natural killer (NK) cells. Using integrated TIMING and single cell RNA sequencing, we identified a population of killer NK cells that perform ADCC efficiently and correlate with clinical responses to trastuzumab. From functional validation of the killer signature, we discovered that 1) inhibiting CD16 shedding does not improve ADCC and 2) killers upregulate interferons which can be stimulated with the STING agonist, 2'3'-cGAMP, to accelerate tumor killing through increased ADCC-mediated degranulation. We demonstrate that knockouts of the degranulating marker, NKG7, abolished lytic granule exocytotsis, highlighting the essential role of NKG7 in ADCC.

Collectively, our findings uncovered unique cytotoxic features associated with anti-tumor efficacy by immune therapies, advancing strategies to improve cancer therapeutics.
[Engineered For What's Next]


-------------- next part --------------
An HTML attachment was scrubbed...
URL: http://Bug.EGR.UH.EDU/pipermail/engi-dist/attachments/20250403/a1555f94/attachment-0001.html 
-------------- next part --------------
A non-text attachment was scrubbed...
Name: image001.png
Type: image/png
Size: 22744 bytes
Desc: image001.png
Url : http://Bug.EGR.UH.EDU/pipermail/engi-dist/attachments/20250403/a1555f94/attachment-0002.png 
-------------- next part --------------
A non-text attachment was scrubbed...
Name: image002.png
Type: image/png
Size: 5699 bytes
Desc: image002.png
Url : http://Bug.EGR.UH.EDU/pipermail/engi-dist/attachments/20250403/a1555f94/attachment-0003.png