In vivo methods for identifying cancer-associated immunotherapy targets

An in vivo method of identifying a cancer cell modulator of response to an anti-cancer immunotherapy, comprising:

• a) obtaining at least a first population of cancer cells, wherein the cancer cells are syngeneic to a first and second subject, wherein the first subject is immunocompetent and the second subject is immuno-incompetent;
• b) obtaining at least a second population of cancer cells, wherein the at least first population of cancer cells are genetically engineered to comprise at least one genetic modification;
• c) transplanting a portion of the second population of cancer cells into the first subject;
• d) administering at least one immunotherapy to the first subject;
• e) determining the representation of the at least one genetic modification from at least one population of cancerous cells propagated in the first subject from said transplanted portion of the second population of cancer cells relative to the representation of the at least one genetic modification from the portion of the second population of cancer cells prior to transplantation;
• f) repeating steps c) through e) with the second subject;
• and
• g) determining at least one genetic modification having a significantly modulated relative representation in the first subject and not having a significantly modulated relative representation in the second subject, thereby identifying a cancer cell modulator of response to an anti-cancer immunotherapy.