IN VITRO METHOD FOR THE PROGNOSIS OF PROGRESSION OF A CANCER AND OF THE OUTCOME IN A PATIENT AND MEANS FOR PERFORMING SAID METHOD
The present invention relates to the prognosis of the outcome of a cancer in a patient, which prognosis is based on the quantification of one or several biological markers that are indicative of the presence of, or alternatively the level of, the adaptive immune response of said patient against said cancer.
1 - 19 . (canceled)
20 . An in vitro method for the prognosis of survival time of a patient suffering from cancer, comprising
a) measuring, in a tumor sample, an amount of mRNA encoding at least one biological marker selected from the group consisting of GNLY, LAG3, CXCL13, PF4, CXCL9, REN, integrin alpha E (ITGAE), CCL5, TSLP, IL17, GZMH, PROM1, IHH, interferon gamma (IFNG), and VEGF;
b) quantifying a level of gene expression of said at least one biological marker based on said amount of mRNA measured in said measuring step;
c) comparing said level of gene expression with a corresponding predetermined reference value, wherein said predetermined reference value is correlated with a specific prognosis of survival time of patients suffering from said cancer; and
d) providing a prognosis of survival time for said patient.
21 . The in vitro method of claim 1 , wherein
a favorable prognosis is provided when said at least one biological marker is GNLY, LAG-3, CXCL13, CXCL9, integrin alpha E, CCL5, GZMH, or IFNG and said level of gene expression is higher than said corresponding predetermined cut-off reference value; and wherein
a poor prognosis is provided when said at least one biological marker is PF4, REN, TSLP, IL17, PROM1, IHH, or VEGF and said level of gene expression is higher than said corresponding predetermined cut-off reference value.
22 . The in vitro method of claim 1 , wherein said step of measuring mRNA is performed by
immobilizing said mRNA on a solid surface;
contacting immobilized mRNA with a polynucleotide probe specific for binding to said mRNA; and
detecting an mRNA-probe complex.
23 . The in vitro method of claim 1 , wherein said step of measuring mRNA is performed by
immobilizing said polynucleotide probe specific for binding to said mRNA to a solid support;
contacting immobilized probe with said mRNA; and
detecting an mRNA-probe complex.
24 . The in vitro method of claim 1 , wherein said step of measuring mRNA is performed by
annealing polynucleotide primers that specifically hybridize to said mRNA;
amplifying said mRNA, and detecting and quantifying amplification products;
reverse transcribing said mRNA to form cDNA; and
measuring an amount of said cDNA.
25 . The in vitro method according to claim 1 , wherein said tumor tissue sample is selected from the group consisting of (i) a global primary tumor sample, (ii) a tissue sample from the center of the tumor, (iii) a tissue sample from the invasive margin of the tumor, (iv) a sample from the lymph nodes located in closest proximity to the tumor, (v) a sample from a tumor biopsy performed prior to surgery, and (vi) a sample from a distant metastasis.
26 . The in vitro method according to claim 1 , wherein said at least one biological marker includes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 biological markers.
27 . The in vitro method according to claim 1 , wherein step b) is performed by quantifying at least 2 distinct biological markers selected from the gene combinations listed in Table 8.
28 . A kit for the prognosis of progression of a cancer in a patient, wherein said kit comprises means for quantifying at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 distinct biological markers selected from the group consisting of GNLY, LAG3, CXCL13, PF4, CXCL9, REN, integrin alpha E (ITGAE), CCL5, TSLP, IL17, GZMH, PROM1, IHH, IFNG, and VEGF.