Journal
ADVANCED SCIENCE
Volume 8, Issue 14, Pages -Publisher
WILEY
DOI: 10.1002/advs.202100712
Keywords
immunotherapy; myeloid‐ derived suppressive cells (MDSCs); multifunctional nanodrug; photodynamic therapy; PI3Kγ inhibitor
Categories
Funding
- National Nature Science Foundation of China [81472825, 51933011, 31971296]
- Key Program of Science and Technology of Guangdong Province [2017B020227009]
- Key Areas Research and Development Program of Guangzhou [202007020006]
- Outstanding Young Talents Support Program of The Third Affiliated Hospital of Sun Yat-sen University
Ask authors/readers for more resources
By combining immunogenic photodynamic therapy with MDSC-targeting immunotherapy, the synergistic treatment effectively inhibits tumor growth while promoting immune responses to prevent tumor recurrence and metastasis.
An ideal tumor treatment is supposed to eliminate the primary tumor and simultaneously trigger the host antitumor immune responses to prevent tumor recurrence and metastasis. Herein, a liposome encapsulating phosphoinositide 3-kinase gamma (PI3K gamma) inhibitor IPI-549 and photosensitizer chlorin e6 (Ce6), denoted by LIC, is prepared for colon cancer treatment. LIC internalized into CT26 cells generates reactive oxygen species (ROS) under laser irradiation to cause immunogenic tumor cell death, during which immunostimulatory signals such as calreticulin are released to further induce T lymphocyte-mediated tumor cell killing. Meanwhile, IPI-549 transported by liposome can inhibit PI3K gamma in the myeloid-derived suppressive cells (MDSCs), resulting in downregulation of arginase 1 (Arg-1) and ROS to promote MDSCs apoptosis and reduce their immunosuppressive activity to CD8(+) T cells. LIC-mediated immunogenic photodynamic therapy synergizes with MDSCs-targeting immunotherapy, which significantly inhibits tumor growth via facilitating the dendritic cell maturation and tumor infiltration of CD8(+) T cells while decreasing the tumor infiltration of immunosuppressive regulatory T cells, MDSCs, and M2-like tumor-associated macrophages. Moreover, the synergistic therapy increases the number of effector memory T cells (T-EM) in spleen, which suggests a favorable immune memory to prevent tumor recurrence and metastasis. The Ce6 and IPI-549-coloaded multifunctional nanodrug demonstrates high efficacy in colon cancer treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available