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. A method for treating a patient suffering from a cancer, comprising the steps of:
a) evaluating the intra-tumor adaptative 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 adaptative immune of said patient against cancer, wherein said at least two biological markers are CD8 and CD3;
b) administering an anti-cancer agent to the patient;
c) evaluating the intra-tumor adaptative 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 adaptative immune of said patient against cancer;
d) comparing the levels of said at least two biological markers quantified in step a) with the levels of said at least two biological markers quantified in step c);
e) administering to the patient:
an immuno-stimulatory agent when the level of CD8 has not increased between step a) and step c); and/or
an immuno-stimulatory agent when the level of CD3 has not increased between step a) and step c).
2. The method according to claim 1 , wherein step
e) further comprises administering to said patient an adjuvant therapy.
3. The method according to claim 1 , wherein said immuno-stimulatory agent is an immuno-stimulating cytokine or chemokine.
4. The method according to claim 3 , wherein said cytokine or chemokine is selected from the group consisting of IL-1α, 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 cancer is a solid cancer.
9. The method of claim 1 , wherein the cancer is selected from the group consisting of colorectal cancer, colon cancer, rectum cancer, pancreatic cancer, gastrointestinal carcinoid tumors, stomach cancer, skin cancer, melanoma, lung cancer, bladder cancer, breast cancer, bile duct cancer, laryngeal cancer, hypolaryngeal cancer, nasal cavity cancer, paranasal sinus cancer, nasopharyngeal cancer, oral cavity cancer, oropharyngeal cancer, and salivary gland cancer.
10. The method of claim 1 , wherein the cancer is colorectal cancer.
11. The method according to claim 1 , wherein said anti-cancer agent is a chemotherapeutic agent.
12. The method according to claim 1 , wherein said anti-cancer agent is an immunotherapeutic agent.