title: Calreticulin Expression in Human Non-Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis.
abstract: A high density of tumor-infiltrating mature dendritic cells (DC) and CD8(+) T cells correlates with a positive prognosis in a majority of human cancers. The recruitment of activated lymphocytes to the tumor microenvironment, primed to recognize tumor-associated antigens, can occur in response to immunogenic cell death (ICD) of tumor cells. ICD is characterized by the preapoptotic translocation of calreticulin (CRT) from the endoplasmic reticulum (ER) to the cell surface as a result of an ER stress response accompanied by the phosphorylation of eukaryotic initiation factor 2α (eIF2α). We conducted a retrospective study on two independent cohorts of patients with non-small cell lung cancer (NSCLC) to investigate the prognostic potential of CRT. We report that the level of CRT expression on tumor cells, which correlated with eIF2α phosphorylation, positively influenced the clinical outcome of NSCLC. High CRT expression on tumor cells was associated with a higher density of infiltrating mature DC and effector memory T-cell subsets, suggesting that CRT triggers the activation of adaptive immune responses in the tumor microenvironment. Accordingly, patients with elevated CRT expression and dense intratumoral infiltration by DC or CD8(+) T lymphocytes had the best prognosis. We conclude that CRT expression constitutes a new powerful prognostic biomarker that reflects enhanced local antitumor immune responses in the lung. Cancer Res; 76(7); 1746-56. ©2016 AACR.
authors: Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. Sotio, Prague, Czech Republic.
authors: Jitka
authors: J
authors: Fucikova
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Etienne
authors: E
authors: Becht
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Kristina
authors: K
authors: Iribarren
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Jeremy
authors: J
authors: Goc
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Romain
authors: R
authors: Remark
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France. Service d'Anatomie-Pathologique, Hôpital Hotel Dieu, AP-HP, Paris, France.
authors: Diane
authors: D
authors: Damotte
authors: Service de Chirurgie Thoracique, Hôpital Cochin, AP-HP, Paris, France.
authors: Marco
authors: M
authors: Alifano
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Priyanka
authors: P
authors: Devi
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Jerome
authors: J
authors: Biton
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Claire
authors: C
authors: Germain
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France. Service d'Anatomie-Pathologique, Hôpital Hotel Dieu, AP-HP, Paris, France.
authors: Audrey
authors: A
authors: Lupo
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Wolf Herve
authors: WH
authors: Fridman
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Marie-Caroline
authors: MC
authors: Dieu-Nosjean
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France. Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Paris, France. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors: Guido
authors: G
authors: Kroemer
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France.
authors: Catherine
authors: C
authors: Sautès-Fridman
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes-Paris 5, UMRS1138, Paris, France. isabelle.cremer@crc.jussieu.fr.
authors: Isabelle
authors: I
authors: Cremer
mesh_terms: D037282:Calreticulin / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D015331:Cohort Studies; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000378:metabolism
chemical_list: D037282:Calreticulin