About the Cover
Cancer treatments have traditionally worked best in combination, either by combining multiple chemotherapies or by combining treatment modalities (for example, chemotherapy plus radiation therapy). Immunotherapies have had some spectacular successes, but usually work well in only a small percentage of patients. A combination strategy, cryoablation plus anti–CTLA-4 blockade was tested for its safety as a pre-operative therapy in early stage breast cancer, and Page et al. used deep sequencing of T-cell receptors (TCRs) to measure the quantity and diversity of immune responses. They found that DNA sequencing could be more sensitive than histological stains in determining intratumoral T cell presence, and that the combination of cryo-immunotherapy, rather than either therapy alone, induced more T-cell clones to expand dramatically within the tumor bed. Read more in Page et al., starting on page 835 of this issue. The high-resolution multispectral immunofluorescence image on the right shows immune cell infiltration in an early stage breast cancer specimen (photo from Carmen Ballesteros-Merino of the Bernard Fox lab, in collaboration with David Page). Artwork by Lewis Long.