Activated CD8+ T cell extracellular vesicles preventtumour progression by targeting of lesional mesenchymal cells

Naohiro Seo, YoshitakaShirakura et al.

NATURE COMMUNICATIONS  (2018)

Recently, it has been reported that CD8+ T cells transmigrateinto tumour lesions by releasing granzyme B or by other unknown mechanism to leadto tumour cell or tumour stromal cells killing, modulation of tumour angiogenesisand/or vascularization. Tumour stroma is formed by various infiltrating and locally differentiatedcell populations including cancer-associated fibroblasts (CAFs) and mesenchymalstem cells (MSCs). During the malignant transformation process, tumour cellsacquire mesenchymal-like features that enable metastatic migration into bloodvessels, which was mainly caused by extracellular vesicles (EV)-dependent actions between tumour cells and tumour stromalcells such as MSCs and CAFs.

In this study, they investigated depletion of mesenchymal stroma in CD8 EV-treated tumour. And reduced viability of cultured MSC bytreatment with CD8 EV in vitro. As a result, CD8 EV Prevents tumourinvasion and metastasis and destructs tumour stroma.Thus, CD8+T cells have been identified to protect tumour progression by EV mediateddepletion of mesenchymal tumour stromal cells.

ONECUT2 is a targetable master regulator of lethalprostate cancer that suppresses the androgen axis

Mirja Rotinen, Sungyong You et al.

NATURE MEDICINE(2018)

Patients with localized prostate cancer can survivefor many years after surgery. But for patients whose tumor have spread to otherparts of the body and are resistant to hormonal therapies, the prognosis ispoor. There is a need to develop new strategies to prevent prostate cancer frombecoming fatal for patients who have metastatic cancer and are resistant to normonaltherapies.

The Freeman team found that ONECUT2 interferes theactivity of the androgen receptor protein. This process can make the growth of prostatecancer become less dependent on androgens. At the same time, ONECUT2 promotessome cancer cells to become more aggressive and resistant to hormone therapy.Its dual role can help to explain why prostate cancers can escape from hormonetherapy. Researchers used human tissue samples, drug databases and laboratoryanimals to identify a compound called CSRM617 that can block ONECUT2. Theyfound that CSRM617 significantly reduced metastases of prostate cancer in mice.

These findings suggest that ONECUT2 displacesAR-dependent growth and survival mechanisms in many cases where AR remainsexpressed. ONECUT2 is also a potential drug target in the metastatic phase of aggressiveprostate cancer.

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