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Deep abscopal response to radiotherapy and anti-PD-1 in an oligometastatic melanoma patient with unfavorable pretreatment immune signature
- Source :
- Cancer Immunology, Immunotherapy
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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. Electronic supplementary material The online version of this article (10.1007/s00262-020-02587-8) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
Abscopal effects
Cancer Research
Chemokine
medicine.medical_treatment
Programmed Cell Death 1 Receptor
Immunology
Epitopes, T-Lymphocyte
CD8-Positive T-Lymphocytes
Radiosurgery
Epitope
Hypofractionated radiotherapy
03 medical and health sciences
0302 clinical medicine
Immune system
medicine
Humans
Immunology and Allergy
Immune signatures
Melanoma
Aged
030304 developmental biology
0303 health sciences
biology
business.industry
medicine.disease
Immune checkpoint
ddc
Blockade
Radiation therapy
Oncology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Original Article
Immunotherapy
business
Immune checkpoint blockade
CD8
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....500623d091e36c2622d22eb20d3cc57a