Hung Trinh, Senior VP of Operations at Seneca Therapeutics, shared a post on LinkedIn about a paper by published in Science Advances:
“Novel Immunotherapy Combination Destroys Colorectal Liver Metastases
University of California, San Francisco researchers disrupt tumor immune environment with LIGHT/anti-CTLA-4 therapy in preclinical models.
The combination functions by homing tumor-infiltrating lymphocytes, inducing tumor antigen-specific T cells, and reversing T cell exhaustion. Whereas both LIGHT overexpression and anti-CTLA-4 increase tumor-promoting macrophages, the combination eliminates this population.
The ability of LIGHT overexpression combined with CTLA-4 inhibition to reverse T cell exhaustion and myeloid cell suppression is supported by analysis of complementary patient cohorts and has strong clinical relevance, especially given that liver metastases contribute to immunotherapy resistance across various cancer types.
What was not previously fully understood is how LIGHT overexpression acts on the TME of MSS (‘cold’) CRLMs and affects the balance of tumor-promoting and tumor-suppressive elements, nor how to overcome this. Furthermore, to have potential for patient treatment, complete tumor regressions are necessary and have not yet been achieved in MSS CRLMs.
On the basis of CTLA-4+ TILs specifically trafficking to CRLMs, a combination of LIGHT with anti–CTLA-4 ICB could provide this balance. Thus, the combination strategy was evaluated, and the mechanism of clinical response was determined.”
Title: Combination LIGHT overexpression and checkpoint blockade disrupts the tumor immune environment, impacting colorectal liver metastases
Authors: Bridget P. Keenan, Guilin Qiao, Nicholas Kunda, Lyonell Kone, Sophia M. Guldberg, Letizia Todeschini, Prabhakaran Kumar, Tommaso Pollini, Sophia Hernandez, Jianzhong Qin, Lawrence Fong, Matthew H. Spitzer, Bellur S. Prabhakar, and Ajay V. Maker
You can read the Full Article in Science Advances.
More posts featuring Hung Trinh.