TY - JOUR
T1 - Deep abscopal response to radiotherapy and anti-PD-1 in an oligometastatic melanoma patient with unfavorable pretreatment immune signature
AU - Watanabe, Tsubasa
AU - Firat, Elke
AU - Scholber, Jutta
AU - Gaedicke, Simone
AU - Heinrich, Corinne
AU - Luo, Ren
AU - Ehrat, Nicolas
AU - Multhoff, Gabriele
AU - Schmitt-Graeff, Annette
AU - Grosu, Anca Ligia
AU - Abdollahi, Amir
AU - Hassel, Jessica C.
AU - von Bubnoff, Dagmar
AU - Meiss, Frank
AU - Niedermann, Gabriele
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB). We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T cells and high expression of T cell-attracting chemokines. This patient rapidly mounted a complete response, now ongoing for more than 4.5 years. Patient 2 exhibited low CD8+ T cell infiltration and high expression of immunosuppressive arginase. After the first SBRT, his non-irradiated metastases did not regress and new metastases occurred although neoepitope-specific and differentiation antigen-specific CD8+ T cells were detected in the blood. A second SBRT after 10 months on anti-PD-1 induced a radiologic complete response correlating with an increase in activated PD-1-expressing CD8 T cells. Apart from a new lung lesion, which was also irradiated, this deep abscopal response lasted for more than 2.5 years. However, thereafter, his disease progressed and the activated PD-1-expressing CD8 T cells dropped. Our data suggest that oligometastatic patients, where a large proportion of the tumor mass can be irradiated, are good candidates to improve ICB responses by RT, even in the case of an unfavorable pretreatment immune signature, after progression on anti-PD-1, and despite advanced age. Besides repeated irradiation, T cell epitope-based immunotherapies (e.g., vaccination) may prolong antitumor responses even in patients with unfavorable pretreatment immune signature.
AB - Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB). We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T cells and high expression of T cell-attracting chemokines. This patient rapidly mounted a complete response, now ongoing for more than 4.5 years. Patient 2 exhibited low CD8+ T cell infiltration and high expression of immunosuppressive arginase. After the first SBRT, his non-irradiated metastases did not regress and new metastases occurred although neoepitope-specific and differentiation antigen-specific CD8+ T cells were detected in the blood. A second SBRT after 10 months on anti-PD-1 induced a radiologic complete response correlating with an increase in activated PD-1-expressing CD8 T cells. Apart from a new lung lesion, which was also irradiated, this deep abscopal response lasted for more than 2.5 years. However, thereafter, his disease progressed and the activated PD-1-expressing CD8 T cells dropped. Our data suggest that oligometastatic patients, where a large proportion of the tumor mass can be irradiated, are good candidates to improve ICB responses by RT, even in the case of an unfavorable pretreatment immune signature, after progression on anti-PD-1, and despite advanced age. Besides repeated irradiation, T cell epitope-based immunotherapies (e.g., vaccination) may prolong antitumor responses even in patients with unfavorable pretreatment immune signature.
UR - http://www.scopus.com/inward/record.url?scp=85083962521&partnerID=8YFLogxK
U2 - 10.1007/s00262-020-02587-8
DO - 10.1007/s00262-020-02587-8
M3 - Journal articles
C2 - 32350591
AN - SCOPUS:85083962521
SN - 0340-7004
VL - 69
SP - 1823
EP - 1832
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 9
ER -