In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-101-PO-101
Abstract:
Background: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for assessment of treatment response poses a challenge for validating novel therapies. In this proof-of-principle study, we evaluate the role of endoscopic ultrasound (EUS)-guided serial fine-needle aspiration biopsies (FNABs) to study the mechanism of action of radiofrequency ablation (RFA). Methods: Patients with stage III inoperable PDAC with prior exposure to gemcitabine were selected into ARDEO (ethically approved Phase-II prospective clinical study of EUS-RFA). Post examination, targeted RF was delivered thrice and sequential FNABs of tumor were taken before and after treatment. Transcriptomic profiling of 6 FNABs from 2 patients was performed using a custom NanoString gene panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes along with immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. Results: RFA treatments were well tolerated without any complications and both patients had stable disease immediately after EUS-RFA. Two-course RFA led to upregulation of CD1E gene (participates in antigen presentation) in both, patient 1 and 2 (4.5 and 3.9-fold) compared to baseline. Patient 1 showed increased expression of T cell genes (CD4 – 8.7-fold, CD8 – 35.7-fold), cytolytic function (6.4-fold) and inflammatory response (8-fold) post-RFA. Greater than 2-fold upregulation of CD274 (PDL1), IDO1, PDCD1 and TNFRSF18 (GITR) was observed post 2nd RFA in both the patients. Further, two-course RFA led to increased PDGFRa (4.5 and 9-fold) in both patients along with enrichment of pCAF subtypes B and C in patient 1 and subtypes A, B and D in patient 2. Immunofluorescence staining revealed expression of PDGFRa, aSMA, VIM, POSTN and MYH11 on patient2-derived CAFs post 1st RFA; validated by immunoblotting. Finally, RFA led to downregulation of classical PDA subtype in both patients. Conclusions: This feasibility study validates longitudinal sampling by EUS-FNABs as an appropriate research tool to study tumor microenvironmental changes associated with local pancreatic immunomodulatory techniques like RFA. Citation Format: Krisha Desai, Patrick Varun Lawrence, Christopher Wadsworth, Nagina Mangal, Nagy Habib, Anguraj Sadanandam, Mikael Sodergren. Characterization of longitudinally collected fine needle aspiration biopsies of pancreatic ductal adenocarcinoma upon endoscopic ultrasound guided radiofrequency ablation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-101.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.PANCA21-PO-101
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2021
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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