Immunological Gene Signature Associated With the Tumor Microenvironment of Pancreatic Cancer After Neoadjuvant Chemotherapy.

Abstract:

OBJECTIVES:Neoadjuvant chemotherapy (NAC) has improved overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but its effects on immune gene signatures are unknown. Here, we examined the immune transcriptome after NAC for PDAC. METHODS:Resected tumor specimens were obtained from 140 patients with PDAC who received surgery first (n = 93) or NAC (n = 47). Six patients were randomly selected from each group, and RNA was extracted from tumor tissues. We compared 770 immune-related genes among the 2 groups using nCounterPanCancer Immune Profiling (NanoString Technologies, Seattle, Wash). Gene clusters were classified into 14 immune function groups based on gene ontology argolism by nSolver 4.0 software (NanoString Technologies), and corresponding immune cell function scores were compared. RESULTS:Eleven genes (LY86, SH2D1A, CD247, TIGIT, CR2, CD83, LAMP3, CXCR4, DUSP4, SELL, and IL2RA) were significantly downregulated in the NAC group. Gene expression analysis showed that the functions of regulatory T cells, B cells, and natural killer CD56 dim cells were significantly decreased in the NAC group. CONCLUSIONS:Neoadjuvant chemotherapy may suppress regulatory T cells and B-cell function in the PDAC microenvironment. The 11 identified genes could be useful for predicting the efficacy of NAC and could be therapeutic targets for PDAC.

journal_name

Pancreas

journal_title

Pancreas

authors

Hane Y,Tsuchikawa T,Nakamura T,Hatanaka KC,Saito T,Tanaka K,Nakanishi Y,Asano T,Noji T,Okamura K,Shichinohe T,Yokota I,Hatanaka Y,Hirano S

doi

10.1097/MPA.0000000000001665

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1240-1245

issue

9

eissn

0885-3177

issn

1536-4828

journal_volume

49

pub_type

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