Engineering immunity to tumor elements

2016

Challenge

The immune system effectively recognizes tumors as foreign elements and fights them. Cancer cells, however, find ways to avoid being attacked by the immune system. To enable the body to effectively remove cancerous cells, the immune system must get past cancer cells' defense mechanisms.

Advance

IRP researchers led by Nicholas Restifo, M.D., have demonstrated how two elements that are common in the body, oxygen and potassium, suppress immune activity and create opportunities for tumors to grow. In animal studies, Restifo and his colleagues have shown that it is possible to engineer antitumor immune cells to be less sensitive to the effects of potassium or oxygen, which makes them more effective in places where cancer cells might otherwise grow unopposed.

Impact

These findings hold promise for designing more effective cancer immunotherapies. It may be possible to empower patients’ immune cells using drugs or genetic manipulation targeting these elemental processes.

Publications

Clever D, Roychoudhuri R, Constantinides MG, Askenase MH, Sukumar M, Klebanoff CA, Eil RL, Hickman HD, Yu Z, Pan JH, Palmer DC, Phan AT, Goulding J, Gattinoni L, Goldrath AW, Belkaid Y, Restifo NP. (2016). Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche. Cell. 166(5):1117-1131.e14.

Eil R, Vodnala SK, Clever D, Klebanoff CA, Sukumar M, Pan JH, Palmer DC, Gros A, Yamamoto TN, Patel SJ, Guittard GC, Yu Z, Carbonaro V, Okkenhaug K, Schrump DS, Linehan WM, Roychoudhuri R, Restifo NP. (2016). Ionic immune suppression within the tumour microenvironment limits T cell effector functionNature. 537(7621):539-543.