Calreticulin expression: Interaction with the immune infiltrate and impact on survival in patients with ovarian and non-small cell lung cancer.
Loss of expression of calreticulin (CALR) has been detected by immunohistochemistry in a fraction of non-small cell lung cancers (NSCLC) and has been demonstrated to have a major negative prognostic impact on overall patient survival. Here, we analyzed the impact of CALR expression levels detected by microarray finding a positive correlation between CALR and the expression of a metagene indicating the presence of cytotoxic T lymphocytes (CTL) in NSCLC and ovarian cancer. In addition, we detected a positive correlation with a metagene suggestive of activated dendritic cell (aDC) infiltration in ovarian cancer. Combination of two parameters (CALR + DC (dendritic cell) in NSCL and CALR + aDC in ovarian cancer) or three parameters (CALR + CTL + DC in NSCL and CALR + CTL + aDC in ovarian cancer) had a significant impact on overall patient survival in NSCL (Adenoconsortium) and ovarian cancer (TCGA collection), allowing the stratification of patients in high-risk and low-risk groups. In addition, CALR and aDC alone have a significant impact on overall survival in ovarian cancer. In contrast, in mammary, colorectal and prostate cancer, CALR had no impact on patient survival if analyzed alone or in combination with the immune infiltrate. In addition, CALR correlates with CTL infiltrate in three cancer types (colorectal, breast, ovarian). Altogether, these results support the contention that, at least in some cancers, loss of CALR expression may negatively affect immunosurveillance, thereby reducing patient survival.
Equipe 11 labellisée Ligue contre le Cancer, Center de Recherche des Cordeliers, INSERM U 1138, 15 rue de l'Ecole de Médecine, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'Ecole de Médecine, Paris, France; Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, Paris, France.
Gautier
G
Stoll
Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'Ecole de Médecine, Paris, France; Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, Paris, France; Laboratory "Cancer, Immune control and escape," Center de Recherche des Cordeliers, INSERM U 1138, 15 rue de l'Ecole de Médecine, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.
Kristina
K
Iribarren
Department of Medical Oncology, Gustave Roussy Cancer Campus (GRCC) , 114 rue Edouard Vaillant , Villejuif, France.
Judith
J
Michels
Department of Medical Oncology, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, France; Laboratory 'Predictive Biomarkers and New Therapeutic Strategies in Oncology' INSERM U981, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, Villejuif, France.
Alexandra
A
Leary
Université Paris Sud, Université Paris Saclay, Kremlin Bicêtre, France; Institut National de la Santé Et de la Recherche Medicale (INSERM), U1015, GRCC, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.
Laurence
L
Zitvogel
Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'Ecole de Médecine, Paris, France; Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, Paris, France; Laboratory "Cancer, Immune control and escape," Center de Recherche des Cordeliers, INSERM U 1138, 15 rue de l'Ecole de Médecine, Paris, France.
Isabelle
I
Cremer
Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'Ecole de Médecine, Paris, France; Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, 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.
Guido
G
Kroemer
Calreticulin; colorectal cancer; cytotoxic T lymphocytes; dendritic cell; immunosurveillance; mammary carcinoma; non-small cell lung cancer; ovarian cancer; prostate cancer