Methods and compositions for prognosis and treatment of cancers
The invention provides methods of using expression levels of one or more immune cell gene signatures and/or combinations of immune cell gene signatures as selection criteria for selecting a patient having cancer for treatment with an immunotherapy. The invention further provides methods for selecting a patient having cancer who may benefit from a particular immunotherapy, such as an activating immunotherapy or a suppressing immunotherapy and administering to the patient the activating immunotherapy or suppressing immunotherapy to treat the cancer.
1. A method of selecting treating a human patient having non-squamous non-small cell lung cancer (NSCLC), the method comprising:
(i) determining the expression level of an immune cell gene signature in a tumor sample obtained from the patient, the immune cell gene signature comprising the following gene signature set:
ITGAM, ITGAX, CD1C, and CLEC4C
wherein an increase in the level of expression of each member of the immune cell gene signature relative to a median level identifies the patient for treatment with an immunotherapy; and
(ii) administering the immunotherapy to the patient.
2. The method of claim 1 , wherein the expression level of ITGAM, ITGAX, CD1C, and CLEC4C is correlated with the presence of myeloid cells in a tumor microenvironment of the tumor sample.
3. The method of claim 1 , further comprising determining the ratio of Teff to Treg cells.
4. The method of claim 3 , wherein if the ratio of Teff to Treg is high, the patient will likely benefit from an immunotherapy.
5. The method of claim 3 , wherein if the ratio of Teff to Treg is low, the patient will likely benefit from an immunotherapy.
6. The method of claim 1 , wherein the determining is carried out prior to administering the immunotherapy in order to provide a patient with a pre-administration prognosis for response.
7. The method of claim 1 , wherein the non-squamous NSCLC is primary, advanced, refractory, or recurrent.
8. The method of claim 1 , wherein expression of the immune cell gene signature in the tumor sample obtained from the patient is detected by measuring mRNA.
9. The method of claim 1 , wherein the immunotherapy enhances tumor immunogenicity.
10. The method of claim 1 , wherein the immunotherapy comprises treatment with a CD28, OX40, GITR, CD137, CD27, ICOS, HVEM, NKG2D, MICA, or 2B4 agonist or treatment with a CTLA-4, PD-1 axis, TIM-3, BTLA, VISTA, LAG-3, B7H4, CD96, TIGIT, or CD226 antagonist.
11. The method of claim 10 , wherein the immunotherapy comprises treatment with a PD-1 axis binding antagonist.
12. The method of claim 11 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist, a PD-1 binding antagonist, or a PD-L2 binding antagonist.
13. A method of treating a human patient having non-squamous NSCLC, the method comprising administering an immunotherapy to the patient, wherein the expression level of an immune cell gene signature in a tumor sample obtained from the patient has been determined to have an increase in the level of expression of each member of the immune cell gene signature relative to a median level, the immune cell gene signature comprising the following gene signature set: ITGAM, ITGAX, CD1C, and CLEC4C.