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Neoadjuvant chemoradiotherapy of pancreatic cancer induces a favorable immunogenic tumor microenvironment associated with increased major histocompatibility complex class I‐related chain A/B expression
Author(s) -
Murakami Takashi,
Homma Yuki,
Matsuyama Ryusei,
Mori Ryutaro,
Miyake Kentaro,
Tanaka Yusaku,
Den Kanechika,
Nagashima Yoji,
Nakazawa Masatoshi,
Hiroshima Yukihiko,
Ueda Michio,
Tanaka Kuniya,
Hoffman Robert M.,
Bouvet Michael,
Endo Itaru
Publication year - 2017
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.24681
Subject(s) - medicine , tumor microenvironment , chemoradiotherapy , pancreatic cancer , major histocompatibility complex , cancer research , cancer , oncology , immunology , immune system , tumor cells
Background Damage‐associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor‐infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. Methods NACRT was administered to 51 patients with borderline‐resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer. Resected specimens were analyzed for the presence of DAMPs, major histocompatibility complex class I‐related chain A/B (MICA/B), and CD8 + TILs, CD4 + TILs, and forkhead box P3 positive (Foxp3 + ) TILs. The Treg/TIL ratio was obtained by dividing the number of Foxp3 + TILs, a surrogate for regulatory T cells, by the sum of CD8 + and CD4 + TILs. Results Overexpression of calreticulin, Hsp70, and MICA/B were all significantly correlated with NACRT administration. In the NACRT group, high MICA/B expression was associated with a low Treg/TIL ratio, indicating a favorable immunogenic tumor microenvironment. Patients with a lower Treg/TIL ratio had longer survival. Conclusions Overexpression of MICA/B, a component of DAMPs induced by NACRT, may play an important role in acquiring a favorable immune response for pancreatic cancer which contributes to longer survival, suggesting the potential of immunotherapy of this recalcitrant disease, especially for patients with overexpression of DAMPs.