Abstract
Pancreatic ductal adenocarcinoma (PDAC) has dismal 5-year survival (<9%). We hypothesize that exposure of tumors to conventional therapies may preferentially modulate immune biomarkers in the tumor microenvironment in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. Total expression of immunologically relevant transcripts and spatially resolved expression of immunologically relevant proteins was quantitated using multiplexed methods (NanoString nCounter and GeoMX platforms). This analysis identified numerous differentially expressed transcripts associated with the type of neoadjuvant therapy received. Moreover, we identified significant alterations in the expression and/or spatial distribution of immunologically relevant proteins in different regions (tumor cell rich, immune cell rich, stromal cell rich) of the tumor microenvironment. These data provide insight into the immunological effects of clinically relevant neoadjuvant therapy for resectable/borderline-resectable PDAC by describing significant differences in the expression of key immunologic biomarkers within the PDAC microenvironment that were associated with the type of treatment patients received prior to surgical resection. This represents a comprehensive analysis of numerous biomarkers conducted on the PDAC microenvironment. This work may guide strategic new combination therapies for pancreatic cancer.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is noted for its poor prognosis, with 5-year survival estimated at only 9% [1]
Six patients had received no treatment for their cancer prior to surgery, six patients received neoadjuvant FOLFIRINOX prior to surgery (FOLFIRINOX), six patients received neoadjuvant FOLFIRINOX followed by stereotactic body radiotherapy (SBRT) (F + SBRT) prior to surgery, and six patients received neoadjuvant FOLFIRINOX followed by conventional radiotherapy (F + XRT) prior to surgery
We examined the effects that 1 type of conventional standard of care therapy (FOLFIRINOX, with/ without 2 types of radiotherapy) has on immune biomarkers within the tumor microenvironment
Summary
Pancreatic ductal adenocarcinoma (PDAC) is noted for its poor prognosis, with 5-year survival estimated at only 9% [1]. Surgical resection remains a patient’s best chance at curative therapy when tumors are detected early [3]. Even in successfully resected patients, prognosis remains grim, with median overall survival estimated as less than 23 months [4]. Surgical resection is often combined with chemotherapy and/or radiation therapy [3]. While these conventional therapeutic modalities lead to modest improvement in overall survival, they are by no means curative in most individuals, emphasizing the need for improved therapeutic options
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