A small subset of patients with pancreatic cancer exhibit a T-cell inflamed profile, a finding that could open the door for the potential use of immunotherapies to treat patients diagnosed with this deadly disease.
A team of researchers from TFRI’s Enhanced Pancreatic Cancer Profiling For Individualized Care (EPPIC) published the finding in Clinical Cancer Research (January 2020).
“Pancreatic cancer has always been considered an immunologically cold tumour, which means that there isn’t a lot of antitumor activity,” explains Joan Miguel Romero, an MD PhD student at McGill University and the paper’s first author. “We have found that even in a tumour like this, some patients do exhibit hallmarks of an antitumor T-cell inflamed phenotype, which means they could potentially benefit from immune checkpoint blockade or other immunotherapies.”
To determine what parameters are associated with CD8+ T cell infiltration in these tumours, the team performed gene expression and immunohistochemical analysis on a cohort of 79 primary pancreas tumour samples. This approach allowed them to conclude that T-cell infiltration was directly associated with a distinct panel of four chemokines. Increased expression of these chemokines marked immunohistochemical and transcriptional hallmarks of an antitumour response in an expanded cohort of 113 primary tumors and 107 liver metastases, including gene sets predictive of immunotherapy response in other tumour types.
In the process, the team also found that CD8+ T-cell infiltration was not tied to tumour mutation burden or neoantigen load, which seems to occur in other cancer types.
“We saw that there might be something unique happening in the immune landscape of select pancreas cancer patients that we still need to learn more about,” says Romero.
While there is still a lot of research that needs to be done before immunotherapies show promise in pancreatic cancer patients, the study helps advance our understanding of the basic biology of tumour immunology, which is one of the first steps that can help clarify if, and how, researchers can modify or stratify patients for response to immunotherapy.
“The main takeaway from this paper is that even though pancreas cancer is considered immunologically cold, we shouldn’t be discouraged,” says Romero. “Future studies exploring the underlying immunobiology in tumors, including pancreatic cancer, will help uncover how we can use the immune system to help these patients.
A four-chemokine signature is associated with a T cell-inflamed phenotype in primary and metastatic pancreatic cancer
Joan Miguel Romero, Barbara Grünwald, Gun Ho Jang, Prashant Bavi, Aaditeya Jhaveri, Mehdi Masoomian, Sandra Fischer, Amy Zhang, Robert E. Denroche, Ilinca M. Lungu, Angela De Luca, John M.S. Bartlett, Jing Xu, Niandong Li, Sharon Dhaliwal, Sheng-Ben Liang, Dianne Chadwick, Foram Vyas, Peter Bronsert, Rama Khokha, Tracy L. McGaha, Faiyaz Notta, Pamela S. Ohashi, Susan J. Done, Grainne M. O’Kane, Julie M. Wilson, Jennifer J. Knox, Ashton Connor, Yifan Wang, George Zogopoulos, and Steven Gallinger
The study was partially funded by a Terry Fox Translational Research Program grant to Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC)