TY - JOUR
T1 - Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy
AU - Vitale, Ilio
AU - Sistigu, Antonella
AU - Manic, Gwenola
AU - Rudqvist, Nils Petter
AU - Trajanoski, Zlatko
AU - Galluzzi, Lorenzo
PY - 2019/5
Y1 - 2019/5
N2 - Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies. Here, we explore how tumor-intrinsic factors and immunological processes shape the mutational and antigenic landscape of evolving neoplasms to influence clinical responses to immunotherapy, and propose strategies to achieve robust immunological control of the disease despite disabled immunosurveillance.
AB - Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies. Here, we explore how tumor-intrinsic factors and immunological processes shape the mutational and antigenic landscape of evolving neoplasms to influence clinical responses to immunotherapy, and propose strategies to achieve robust immunological control of the disease despite disabled immunosurveillance.
KW - adoptive cell transfer
KW - antigen presentation
KW - immune checkpoint blockers
KW - mutational load
KW - oncolytic virotherapy
KW - tumor microenvironment
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U2 - 10.1016/j.tcb.2019.01.003
DO - 10.1016/j.tcb.2019.01.003
M3 - Review article
C2 - 30765144
AN - SCOPUS:85061247338
VL - 29
SP - 396
EP - 416
JO - Trends in Cell Biology
JF - Trends in Cell Biology
SN - 0962-8924
IS - 5
ER -