[Immunogenomic aspects of tumor progression]

Abstract

Genomic instability is a hallmark of cancer therefore of the metastatic disease as well. High tumor mutation burden is due to deficiencies of the DNA repair systems and leads to immunosensitivity due to generation of neoantigens. However, APOBEC activation of that system, though increases mutation rate, but causes immunoresistance. Deficient antigen presentation due to HLA class I defects is another major cause of immunoresistance. The contemporary immunotherapies may exploit gene amplification of PD-L1 but if the affected chromosome is damaged IFN activation can be lost, again causing immunoresistance. Since these genetic changes can be generated continuously during tumor progression (the entire metastatic process), it would be necessary to monitor them continuously. On the other hand, since tumors are genetically and phenotypically heterogeneous, multiple sampling would be necessary to obtain a more realistic picture of biomarker expressions.