Abstract:
:Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models. Twenty-one BC patients with ≤6 metastases were treated with 3 daily doses of 10 Gy with SBRT. Blood samples for immune profiling were collected before and after treatment. One month after treatment a third of patients displayed the boosting or even the de novo appearance of polyfunctional CD4+ and CD8+ T cell responses against known BC TAAs (survivin, mammaglobin-A, HER2), through intracellular staining in flow cytometry. Half of patients showed increased numbers of activated natural killer (NK) cells, measured with multispectral flow cytometry, immediately after the first dose of SBRT. Interestingly, high levels of activated NK cells at diagnosis correlated with a longer progression-free survival. BC in vitro models, treated with the same SBRT modality, showed enhanced expression of MHC class-I and class-II, major histocompatibility complex class I-related chain A/B, and Fas molecules, and increased release of pro-inflammatory cytokines, such as IL-1β and TNF-α. Consistently, we noticed enhanced production of perforin by CD4+ T cells when patients' lymphocytes were cultured in the presence of irradiated BC cell line, compared to untreated targets. Besides immunogenic effects, SBRT also enhanced the percentages of circulating regulatory T cells, and increased indoleamine 2,3 dioxygenase and PD-L1 expression in BC in vitro models. These results suggest that SBRT may boost host antitumor immune responses also in an advanced disease setting such as oligometastatic BC, by inducing immunomodulating effects both locally and systemically. However, the concomitant induction of immunosuppressive pathways suggests that a combination with immunotherapy could further enhance the in situ vaccination ability of radiotherapy, possibly further improving the curative potential of SBRT in this subset of patients.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Muraro E,Furlan C,Avanzo M,Martorelli D,Comaro E,Rizzo A,Fae' DA,Berretta M,Militello L,Del Conte A,Spazzapan S,Dolcetti R,Trovo' Mdoi
10.3389/fimmu.2017.01476subject
Has Abstractpub_date
2017-11-06 00:00:00pages
1476issn
1664-3224journal_volume
8pub_type
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00430
更新日期:2014-09-08 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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