Cancer Immunol Res: How Pancreatic Cancer Cells Escape Immunotherapy

January 29, 2021 // -- Pancreatic cancer is one of the deadliest cancers of all cancers, and it can evade immune cell attacks by changing the micro-environment, allowing immune cells to suppress rather than support attacks on tumors.
also found that certain signaling molecules that inhibit the reaction, including a protein called STAT1, may be potential therapeutic targets.
the findings were published in the January 28, 2021 issue of Cancer Immunology Research.
The first evidence that immune attacks induce immunosuppression derived from pancreatic cancer provides a new immunotherapy for this deadly cancer," said Dr. Louis M. Weiner, director of Georgetown Lombardi and lead researcher on the study.
" (Photo: www.pixabay.com) Pancreatic catheter adenocarcinoma (PDAC) accounts for more than 90 percent of all pancreatic cancers and is expected to have nearly 60,000 cases in the United States by 2021.
despite recent significant advances in cancer immunotherapy, cancer rarely responds to such treatments.
of the reasons for this resistance to treatment is the tumor micro-environment of PDAC, which inhibits the immune response that helps attack cancer cells.
Reham Ajina, a student in the Oncology Biology Program at Georgetown University Medical Center, studied mice to explore how T-cells, the immune cells most responsible for identifying and killing cancer cells, trigger anti-tumor responses.
T-cell response is found in many cancers, but is rare in most pancreatic cancer tissues.
The tumor tissue includes not only cancer cells, but also a variety of non-cancerous components, such as immunity, fat and neuron cells, as well as the fibers and blood vessels that make up the tumor's micro-environment," Ajina said.
Normally, T-cells recognize and kill cancer cells, but it appears that malignant pancreatic cells are trying to evade Immune attacks from T-cells by affecting the micro-environment of tumors.
inhibition of this remodeling is a major challenge in trying to treat pancreatic cancer.
" johns Hopkins University and Oak Ridge National Laboratory provide cutting-edge analytical techniques that enable the key process of this remodeling to be visualized in mice.
in addition to finding remodeling and immune escape, the team was able to identify one of the agents of this inhibitory reaction, including an activated protein called signal transduter and transcription activator 1 (STAT1).
hypothesical that STAT1-based signal transductivity could reverse this drug-resistant mechanism.
researchers chose ruxolitinib, an FDA-approved drug that targets STAT signaling paths and can be tested in mice.
, the drug's use overcomes the protective remodeling response of tumors and helps improve the response to immunotherapy.
"Our preclinical studies in mice have shown that ruxolitinib, in combination with other approved immunotherapy, can improve prognostication in pancreatic cancer patients.
promising way to treat invasive cancer, and we hope to be able to test it in clinical trials.
" () Source: Mechanism for how to pancreatic cancer evades immunotherapy explained Original source: Louis M Weiner et al, Antitumor T-cell Immunity Contributes to Pancreatic Cancer Immune Cancer Immune Cancer Immunity Cancer Immunol Res January 28 2021 DOI: 10.1158/2326-6066.CIR-20-0272