Characterizing TILs in Pancreatic NET Liver Metastases

In a conversation with CancerNetwork®, Mauro Cives, MD, outlined the background behind his Investigator Award-winning research project funded by the Neuroendocrine Tumor Research Foundation (NETRF). Collaborating with Anguraj Sadanandam, PhD, FRSB, at the Institute of Cancer Research (ICR), Cives is spearheading an effort to transition pancreatic neuroendocrine tumors (NETs) from "immunologically cold" targets to viable candidates for precision cellular immunotherapy.

Highlighting that former research sought to test whether tumor-infiltrating lymphocytes (TILs) could be extracted from liver metastases of pancreatic NETs, he explained that this hypothesis was confirmed and clinically meaningful, prompting his team to characterize these TILs. One surprising finding Cives unearthed was the presence of memory progenitor stem-like phenotypes in most of these tumors––indicative of predicting antitumor activity.

He further highlighted the finding that these TILs could recognize and dispatch autologous tumors, in addition to the restricting reactivities to immune niches within each mass. In summary, Cives explained that a fraction of these lymphocytes could be used to confer antitumor activity, which led him to initiate his current research examining T-cell receptor (TCR)–based therapies in pancreatic NETs.

Cives is an associate professor of Medical Oncology in the Department of Interdisciplinary Medicine at University of Bari Aldo Moro.

Transcript:

The current research project was submitted by myself and professor Anguraj Sadanandam, PhD, FSRB, and [his team] at the ICR in London. It lies on some fundamental answers that we [found] to our former research questions.

Our former research question was, “Can we isolate tumor-infiltrating lymphocytes from pancreatic NET liver metastases?” The answer to this research question was yes. The following question was, “Are these numbers clinically meaningful?” The answer was, again, yes. Then, we went on characterizing the tumor-infiltrating lymphocytes coming out from the pancreatic NET liver metastasis.

Quite surprisingly, we found that most of them have memory progenitor stem-like phenotypes––they are double negative for CD39 and CD69. This is something that is well known to predict antitumor activity of these T cells when injected back into patients. Moreover, we demonstrated that these tumor-infiltrating lymphocytes were able to recognize and attack autologous tumors and that antitumor reactivities were especially restricted to immune niches rather than dispersed throughout the tumors. What I’m saying here is that not all tumor-infiltrating lymphocytes within pancreatic NET liver metastases are created equally, but a fraction of them is able to exploit antitumor activity against the tumor cells.