Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFNγ Signaling
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Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFNγ Signaling. / Donia, Marco; Harbst, Katja; van Buuren, Marit; Kvistborg, Pia; Lindberg, Mattias F; Andersen, Rikke; Idorn, Manja; Munir Ahmad, Shamaila; Ellebæk, Eva; Mueller, Anja; Fagone, Paolo; Nicoletti, Ferdinando; Libra, Massimo; Lauss, Martin; Hadrup, Sine Reker; Schmidt, Henrik; Andersen, Mads Hald; Thor Straten, Per; Nilsson, Jonas A; Schumacher, Ton N; Seliger, Barbara; Jönsson, Göran; Svane, Inge Marie.
I: Cancer Research, Bind 77, Nr. 17, 01.09.2017, s. 4562-4566.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFNγ Signaling
AU - Donia, Marco
AU - Harbst, Katja
AU - van Buuren, Marit
AU - Kvistborg, Pia
AU - Lindberg, Mattias F
AU - Andersen, Rikke
AU - Idorn, Manja
AU - Munir Ahmad, Shamaila
AU - Ellebæk, Eva
AU - Mueller, Anja
AU - Fagone, Paolo
AU - Nicoletti, Ferdinando
AU - Libra, Massimo
AU - Lauss, Martin
AU - Hadrup, Sine Reker
AU - Schmidt, Henrik
AU - Andersen, Mads Hald
AU - Thor Straten, Per
AU - Nilsson, Jonas A
AU - Schumacher, Ton N
AU - Seliger, Barbara
AU - Jönsson, Göran
AU - Svane, Inge Marie
N1 - ©2017 American Association for Cancer Research.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell-based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8(+) T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I-related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted. Cancer Res; 77(17); 4562-6. ©2017 AACR.
AB - Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell-based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8(+) T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I-related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted. Cancer Res; 77(17); 4562-6. ©2017 AACR.
KW - Journal Article
U2 - 10.1158/0008-5472.CAN-16-3172
DO - 10.1158/0008-5472.CAN-16-3172
M3 - Journal article
C2 - 28655789
VL - 77
SP - 4562
EP - 4566
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 17
ER -
ID: 184877330