In the past decade, there have been considerable advances in the state of the art of immuno-oncology. With the regulatory approval of the T cell checkpoint inhibitory antibody ipilimumab (Yervoy, Bristol-Meyers Squibb), research into novel approaches to modulate the immune response to cancer for therapy has been ushered into a new era. The goal of immuno-oncology is to understand how the components of the immune system interact with the tumor microenvironment, to understand how these interactions contribute to the outcome of the patient, and to modulate the immune response in a way that reduces tumor growth, ideally toward the elimination of tumor cells.
For decades, it has been known that the presence of tumor-infiltrating immune cells is associated with better prognosis of cancer patients. It has been recognized that there are at least three different but related outcomes: elimination, equilibrium, and escape . A highly immunogenic tumor in a healthy, immunocompetent individual will stimulate the innate immune response resulting in acute inflammation, activation of T and B cells, and elimination of the newly arisen tumor. For an individual with a less surveillant immune system, or a less immunogenic tumor, a state of equilibrium may be reached—the immune system would eliminate some but not all tumor cells, leading to reactivation of the immune system, incomplete elimination, and repeated cycling of partial elimination. This equilibrium can be life-long or may be disturbed by changes in the tumor which allow it to avoid immunosurveillance. Tumors which avoid detection by the immune system enter the “escape” phase, in which most cancers are currently diagnosed. Escape from immunosurveillance is due to myriad factors, ranging from downregulation of tumor antigens, loss of human leukocyte antigen molecules, loss of sensitivity to T cell or NK cell lysis, or prevention of the expansion of tumor-antigen specific helper and cytotoxic T cells, leading to an accumulation in suppressive cell populations, inhibiting immunity . The aim of immuno-oncological therapy is to modulate tumor immunity to promote tumor-rejection.
Evaluation of tissue sections to interrogate the immune cell populations within tumor tissue is a critical endpoint to assess the efficacy of immunomodulating cancer therapies. Due to the wide variety of immune cell types and sub-types, multiplex immunofluorescence, which allows for the simultaneous interrogation of multiple cell populations, is required. We employ a series of sophisticated automated image processing algorithms to assess the variety and distribution of immune cells within and around tumor tissue.