Fig. 1

Clonal selection of occult tumor cells harboring T-cell resistance genes. a Tumor at baseline. Circles represent tumor cells and different colors represent intra-tumor heterogeneity with respect to genetic composition. The red tumor cell with a black border harbors T-cell resistance mutations. b Tumor at maximum response. Although the bulk of the tumor is sensitive to immunological assault as a result of anti-PD1 therapy, tumor cells harboring resistance genes are selected for, increasing the ratio of T-cell-resistant to non-resistant cells. c Tumor at progression. The tumor is largely composed of cells containing resistance genes. In the absence of immunological control, metastatic disease is capable of progression and metastasis