In vitro method for the prognosis of progression of a cancer and of the outcome in a patient and means for performing said method
View Patent ↗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. A method for treating a patient suffering from a solid cancer comprising the steps of:
(i) evaluating the intra-tumor adaptive immune status of said patient before administration of an anti-cancer agent by quantifying, in a pre-administration tumor sample, at least two biological markers indicative of the status of the adaptive immune response of said patient against cancer, wherein two of said at least two biological markers are PDCD1LG1 combined with CD8A,
(ii) administering an anti-cancer agent to the patient,
(iii) evaluating the intra-tumor adaptive immune status of said patient after administration of said anti-cancer agent by quantifying in a post-administration tumor sample said at least two biological markers indicative of the status of the adaptive immune response of said patient against cancer,
(iv) comparing the levels of said at least two biological markers quantified in steps (i) with the levels of said at least two biological markers quantified in step (iii),
(v) administering to the patient:
a PDCD1LG1 inhibitor and/or a PDCD1 inhibitor to the patient when the level of PDCD1LG1 has increased between steps (i) and (iii); and/or
an immuno-stimulatory agent when the level of CD8A has not increased between step (i) and step (iii).
2. The method of claim 1 , wherein step (v) further comprises administering to said patient an adjuvant chemotherapy.
3. The method of claim 1 , wherein said immuno-stimulatory agent is an immunostimulating cytokine or chemokine.
4. The method of claim 3 , wherein said cytokine or chemokine is selected from the group consisting of IL-1 α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-7, G-CSF, IL-15, GM-CSF, IFN-γ, CXCL9, CXCL10, Fractalkine, MIG, IFNα, IL-18, IL-12, IL-23 and IL-31.
5. The method of claim 4 , wherein said cytokine or chemokine is selected from the group consisting of IL-2, IFNα, IL-7, IL-15, and GM-CSF.
6. The method of claim 1 , wherein said pre-administration and post-administration tumor samples include either or both tumor center (CT) tissue from the center of the tumor and invasive margin (IM) tissue of the invasive margin of the tumor.
7. The method of claim 6 , wherein said pre-administration and post-administration tumor samples are biopsies.
8. The method of claim 1 , wherein the solid cancer is colorectal cancer.
9. The method according to claim 1 wherein said anti-cancer agent is a chemotherapeutic agent.
10. The method according to claim 1 wherein said anti-cancer agent is an immunotherapeutic agent.