NO. 45

Time:

Friday, Nov. 1 2024, 2:30 p.m.

Location:

Yifu Lecture Hall, North Basic Research Building

Host：

Zihou Deng  (邓子厚)

Chinese Institutes for Medical Research, Beijing

Speaker：

Jing Hu (胡婧)

Investigator

School of Life Sciences

Peking University

TITLE：

Immune Suppressors of Dormant Metastatic Outbreak

ABSTRACT:

Metastasis is the principal cause of death from cancer. For early-stage cancer patients, although no metastasis is detected at the time of diagnosis, metastatic relapse frequently develops after the apparently successful treatment of the primary tumor. These recurrences are thought to be due to disseminated tumor cells (DTCs) that remain dormant in distant organs until triggered to reinitiate metastatic outgrowth. DTCs fluctuate between an immune-evasive quiescent state and a proliferative state liable to immune-mediated elimination. Little is known about how immune system maintains the balance. We used in vivo CRISPR screens of tumour-intrinsic immune regulators in models of indolent lung adenocarcinoma metastasis and identified the stimulator of interferon genes (STING) pathway as a suppressor of metastatic outbreak. STING activity increases in metastatic progenitors that re-enter the cell cycle and is dampened in spontaneous metastases. STING activation in cancer cells suppresses their outgrowth in a T cell- and natural killer cell-dependent manner. Systemic treatment of mice with STING agonists eliminates dormant metastasis and prevents spontaneous outbreaks. Thus, STING provides a checkpoint against the progression of dormant metastasis and a therapeutically actionable strategy for the prevention of disease relapse.

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