In a recent study, adoptive transfer of a tumor-infiltrating lymphocyte (TIL) population that can target a specific tumor mutation has successfully led to the regression of a metastatic epithelial cancer in one patient. The findings suggest that epithelial cancers, which often have a limited amount of mutations, can also elicit mutation-specific T cell responses, and that these can be harnessed to develop personalized T cell–based immunotherapy (Science 344, 641–645, 2014).

Steven Rosenberg and his colleagues performed whole-exome sequencing of lung metastases in the cancer to identify tumor mutations that were then tested to assess the immunoreactivity of patient-derived T cells and determine which mutation was recognized. After selecting for and expanding the desired TILs, their administration along with interleukin-2 into the patient resulted in an initial tumor regression by 2 months, which reached up to 30% decrease in lung and liver metastatic growth at 6 months. After a second T cell transfer, the patient experienced tumor regression by 1 month, with continuing regression at the 6-month follow-up.

Although personalized T cell immunotherapy has been more widely explored in melanoma, there has not been much evidence to suggest its effectiveness against epithelial tumors, the most common cancers found among patients. Future studies may opt to combine these techniques with additional methods that tackle the immunosuppressive environment in patients with cancer to achieve superior responses.