Abstract: A non invasive diagnostic method of pancreatic ductal adenocarcinoma (PDAC) in a subject is provided. The method comprises the step of measuring the level of ?ig-h3 protein in a blood sample wherein the serum level of ?ig-h3 is positively correlated with the risk of having a PDAC. By following studies on 2 distinct cohorts of 20 and 104 of PDAC patients, and on PDAC mouse model, the inventors show that ?ig-h3 can be directly detected in the blood sample and ?ig-h3 is expressed very early in tumorigenesis in pancreatic neoplastic lesions. Also provided is a ?ig-h3 protein, for use in the treatment of PDAC. The inventors found that ?ig-h3 bind directly on CD8+ T cells by reducing their activation and cytotoxic properties. Furthermore, the use of neutralizing ?ig-h3 antibodies in PDAC mouse model reduced tumor growth by enhancing CD8+ T cell anti-tumoral response.

Abstract: To study the mechanism of ?ig-h3 modulation of the anti-tumoral immune response in pancreatic cancer, Inventors took advantage of engineered mouse models of spontaneous pancreatic neoplasia and cancer to evaluate the effect of depleting ?ig-h3 on the modulation of anti-tumor immunity and its subsequent impact on tumour growth alone and in combination with an immune checkpoint inhibitor. This association proved to be effective in vivo in this model showing a synergic effect of the therapeutic combination. Accordingly, the present invention relates to a combination of (i) an immune checkpoint inhibitor, and (ii) a ?ig-h3 antagonist, for simultaneous or sequential use in the treatment of a patient suffering from solid tumor, e.g. a pancreatic cancer. The present invention also provides a ?ig-h3 antagonist, for use in a method for enhancing sensitivity of a patient suffering from a solid tumor to an immune checkpoint inhibitor.

Abstract: The present invention relates to a non invasive diagnostic method of pancreatic ductal adenocarcinoma (PDAC) in a subject said method comprising the step of measuring the level of ?ig-h3 protein in a blood sample wherein the serum level of ?ig-h3 is positively correlated with the risk of having a PDAC. By following studies on 2 distinct cohorts of 20 and 104 of PDAC patients, and on PDAC mouse model, the inventors show that ?ig-h3 can be directly detected in the blood sample and ?ig-h3 is expressed very early in tumorigenesis in pancreatic neoplastic lesions. The present invention also relates to antagonist of ?ig-h3 protein, for use in the treatment of PDAC. The inventors found that ?ig-h3 bind directly on CD8+ T cells by reducing their activation and cytotoxic properties. Furthermore, the use of neutralizing ?ig-h3 antibodies in PDAC mouse model, reduced tumor growth by enhancing CD8+T cell anti-tumoral response.