The spontaneous regression of certain cancers, such as melanoma or renal cell cancer, supports the idea that the immune system is sometimes capable of delaying tumor progression and on rare occasions eliminating a tumor altogether. The term adoptive immunotherapy describes the transfer of immunocompetent cells such as the tumor infiltrating lymphocytes (TILs) to the tumor-bearing host. Adoptive cell transfer (ACT) therapy for patients with cancer relies on the ex vivo generation of highly active tumor, specific lymphocytes, and their administration in large numbers to the autologous host. Presently, ACT therapy however effectively treats only a limited number of patients. Preclinical models have identified a variety of ways to manipulate the host immune environment that increase ACT therapeutic efficacy. These include immunosuppression prior to cell administration and concurrent interleukin 2 administration with the transferred T cells. The developed technology is a method of determining responsiveness to cancer treatment. The method comprises analyzing a frequency of TILs having a CD8+CD28−CD152− signature in a sample of the subject, wherein a frequency of TILs having the CD8+CD28−CD152− signature above a predetermined level is indicative of a positive responsiveness to cancer treatment. The rational depletion and enrichment of selected TIL subpopulations thus also describes a generic approach for the prediction, understanding and control of a cell mixture function.
- Using TIL’s sub-population signature to predict and even control its reactivity against tumors
Applications and Opportunities
- Determining responsiveness to cancer treatment