New target discovered to improve chemotherapy for pancreatic cancer

The pancreatic team of General Surgery department of Peking Union Medical College Hospital (PUMCH), in the past seven years, researched into the micro-environment of pancreatic cancer, and made a breakthrough in discovering a new target to boost the efficacy of chemotherapy. The research won the third prize of the hospital's 2018 Medical Research Award.

Pancreatic cancer, named"the king of cancers," features obscure symptoms, rapid progress and poor prognosis. About 80% of patients have local invasion or metastasis when diagnosed. The effect of both surgery and chemotherapy are unsatisfactory and the five-year survival rate is only 8.4%. Its death rate remains high due to difficult diagnosis in early stage, lack of effective therapies and unclear pathology. This makes all the more important of researching into comprehensive treatments.

More and more evidence in recent years showed that the micro-environment may markedly affect the biological behaviors of pancreatic tumor cells. It is found that pancreatic cancer has a special micro-environment, which consists of extracellular matrix, new vessels, new lymphatic vessels, nerve fibers, immunocytes, fibroblasts, stellate cells and so on. About 50%~70% of them are immunocytes. But they will be "domesticated"by tumor cells, and therefore help with the occurrence of cancer, metastasis and drug resistance. "We research into the interaction between pancreatic cancer cells and immunocytes, which is based on serial models of rats with sound immune systems, patient samples and clinical databank, as well as transcriptome and proteomics databank on the interaction between tumor cells and macrophages built by the team," said Liu Qiaofei from General Surgery.

Guided by President Zhao Yupei and Director Liao Quan, surgeons including Liu looked into new targets based on micro-environment. The team, based on General Surgery, consists members from Pathology, Medical Oncology, Central Lab and others. In seven years, it achieved original research results in the examination of key immunocytes, the domestication of key immunocytes by tumor cells, the leading to drug resistance by key immunocytes and new methods to improve chemotherapy.

Upon analyzing 30 micro-environments around and in cancer tissues, the team found that M2 macrophages claim the largest number there and is in obvious positive correlation with the forming of stem cells, vessels and lymphatic vessels of pancreatic cancer. Tumor cells secrete a large amount of TGF-β1and GM-CSF, leading to invasion and polarization of M2 macrophages which, through maintaining stem cells of tumor, leads to new vessels and lymphatic vessels, and then to Gemcitabine resistance; Gemcitabine stimulates tumor cells, and make them secrete more TGF-β1and GM-CSF, thus forming a vicious circle that leads to more drug resistance.

The research revealed that M2 macrophages, TGF-β1and GM-CSF are independent danger factors in the poor effect of Gemcitabine chemotherapy. Combined blocking of TGF-β1and GM-CSF can improve the Gemcitabine induced micro-environment and improve the drug's efficacy. Several SCI essays have been published on the findings and application filed for national invention patent.

So far, our General Surgery has established a relatively complete system of immunity research on pancreatic cancer. In-depth research on comprehensive treatments is expected to become therapies that finally benefit patients.

Guo Jing contributed to the story.