RT Journal Article
SR Electronic
T1 Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 312
DO 10.1186/s40425-019-0781-z
VO 7
IS 1
A1 Lenka Kasikova
A1 Michal Hensler
A1 Iva Truxova
A1 Petr Skapa
A1 Jan Laco
A1 Lucie Belicova
A1 Ivan Praznovec
A1 Sarka Vosahlikova
A1 Michael J. Halaska
A1 Tomas Brtnicky
A1 Lukas Rob
A1 Jiri Presl
A1 Jan Kostun
A1 Isabelle Cremer
A1 Ales Ryska
A1 Guido Kroemer
A1 Lorenzo Galluzzi
A1 Radek Spisek
A1 Jitka Fucikova
YR 2019
UL http://jitc.bmj.com/content/7/1/312.abstract
AB Background Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, is critical for the host immune system to mount spontaneous and therapy-driven anticancer immune responses. One of such signals, i.e., the exposure of calreticulin (CALR) on the membrane of malignant cells experiencing endoplasmic reticulum (ER) stress, is well known for its role in the activation of immune responses to dying cancer cells. However, the potential impact of CALR on the immune contexture of primary and metastatic high-grade serous carcinomas (HGSCs) and its prognostic value for patients with HGSC remains unclear.Method We harnessed a retrospective cohort of primary (no = 152) and metastatic (no = 74) tumor samples from HGSC patients to investigate the CALR expression in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 302 HGSC samples was used as a confirmatory approach.Results We demonstrate that CALR exposure on the surface of primary and metastatic HGSC cells is driven by a chemotherapy-independent ER stress response and culminates with the establishment of a local immune contexture characterized by TH1 polarization and cytotoxic activity that enables superior clinical benefits.Conclusions Our data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses.