Tumor Immunology, toward a Success Story?

Abstract

PROOF OF IMMUNOSURVEILLANCE AND THE IMMUNOEDITING CONCEPT The beginning of the second millennium marked a turning point for tumor immunity, on the basis of a series of data obtained in mice and in humans. The enhanced susceptibility of immunodeficient mice to the formation of chemically induced or spontaneous tumors clearly showed that the immune system can eliminate nascent tumors (1). A few years later, the investigations showing that high densities of T cells, particularly with a Th1 and cytotoxic polarization, in different locations of a primary tumor, correlate with favorable prognosis for disease-free and overall survival in large series of cancer patients also strongly supported the fact that a natural immune reaction controls invasion and metastasis (2). Most importantly, these results also proved the establishment of a long-term memory against cancers and suggested that it could be reactivated with tumor vaccines. Such breakthroughs had major consequences for the tumor immunity field. They paved the way for a new era for tumor immunology, building on solid foundations, and leaving behind more than 50 years of errances since the concept of tumor immunosurveillance had been put forward. However, tumors develop, invade tissues locally, metastasize in distant organs, and ultimately cancer can be life threatening. During these last 10 years, we also learnt that the immune system “sculpts” tumors, leading to the formation of tumor variants that escape immunosurveillance, and/or inducing suppressive conditions that facilitate tumor outgrowth. Thus, cancer immunotherapy should aim at boosting anti-tumor immunity by breaking immune tolerance or using adoptively transferred expanded tumor infiltrating lymphocytes (already present in the tumor). This last approach has yielded promising results in terminally ill cancer patients.