White Depressed Areas and Tumor Infiltrating Lymphocytes: The Cancer Cure That Lies Within?

This brief overview is inspired by seminal contributions by the late Dr. Martin C. Mihm, Jr. who provided a basis for recognition and better understanding of interactions between lymphocytes (tumor-infiltrating lymphocytes [TILs]) that home to and permeate cancers. In primary melanomas, this phenomenon may produce what Dr. Mihm called white depressed areas, prescient clues to what would fuel future attempts at harnessing anticancer immunity. The critical and sequential TIL attributes of antigenic stimulation, homing, and effector-target cell apoptotic injury herein are briefly reviewed in light of more recent advances in the field of immuno-oncology. The intent is to emphasize how fundamental clinical and histopathological observations, as forged by Dr. Mihm and his associates, have led to critically important prognostic paradigms as well as to translational insights that now have become transformative in the field of cancer immunotherapy.