UCLA Researchers from the Department of Surgery have developed a novel approach to preserve anti-tumor immunity in the peri-operative period through modulation of clinically relevant molecular and cellular targets.
BACKGROUND: Surgical resection with curative intent is a mainstay of treatment for many solid tumors. However, even when the tumor is macroscopically removed, residual microscopic disease can lead to relapse, and eventually death. Moreover, incomplete surgical resections (where visible disease is left behind) are sometimes unavoidable and are associated with accelerated disease progression. Surgery itself also induces systemic immune suppression, which further compromises the body’s ability to eliminate residual cancer cells. This post-operative immunosuppression presents a significant challenge and contributes to poor long-term outcomes. Thus, understanding and targeting the mechanisms driving this post-operative immune suppression is critical for improving cancer treatment strategies incorporating surgical resection.
INNOVATION: UCLA researchers have identified a specific cellular target that drives post-operative immune suppression. Using a novel mouse model simulating incomplete tumor resection, they observed a rapid increase in levels of key immunosuppressive proteins and cell populations following surgery. Importantly, peri-operative inhibition of this newly identified target using existing clinical therapeutics preserved anti-tumor immunity and significantly improved outcomes after surgery. Thus, targeting this protein and its signaling pathways offers a promising strategy for peri-operative immunomodulation in cancer care.
Importantly, the novelty of this invention lies in the discovery of a previously unrecognized therapeutic window and indication for existing FDA-approved therapeutics. UCLA researchers showed that transient, peri-operative blockade of this target preserves anti-tumor immunity and prevents post-surgical immune suppression. This approach allows for both rapid translation using FDA approved biologics and opportunities to develop novel therapeutic modalities based on this innovation.
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ADVANTAGES:
DEVELOPMENT-TO-DATE: UCLA researchers have used a novel mouse model of incomplete tumor resection to illustrate that targeting this protein leads to improved clinical outcomes.
Related Papers (from the inventors only):
Fine SA, Lim SY, Siena NM, de Jesus AB, Goh T, Markus L, Russell TA, Kendal JK, Lofftus SY, Shehata MS, Dao HB, Lee A, Klingbeil KD, Kadera BE, Chmielowski B, Nelson SD, Dry SM, Bernthal NM, Singh AS, Reddy VK, Kalbasi A, Wessel LE, Prins RM, Eilber FR, Eilber FC, McCaw TR, Crompton JG. Incomplete Cancer Surgery Correlates With Loss of Immune Surveillance and Hyper-Progression of Disease. J Surg Oncol. 2025 Sep;132(3):548-555. doi: 10.1002/jso.70023. Epub 2025 Jul 9. PMID: 40631605.
KEYWORDS: Peri-operative therapy, immunotherapy, oncology, tumor, resection, post-operative, immune suppression, surgery, anti-tumor immunity