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Adaptive immune contexture at the tumour site and downmodulation of circulating
myeloid-derived suppressor cells in the response of solitary fibrous tumour
patients to anti-angiogenic therapy
#MMPMID25101565
Tazzari M
; Negri T
; Rini F
; Vergani B
; Huber V
; Villa A
; Dagrada P
; Colombo C
; Fiore M
; Gronchi A
; Stacchiotti S
; Casali PG
; Pilotti S
; Rivoltini L
; Castelli C
Br J Cancer
2014[Sep]; 111
(7
): 1350-62
PMID25101565
show ga
BACKGROUND: Host immunity is emerging as a key player in the prognosis and
response to treatment of cancer patients. However, the impact of the immune
system and its modulation by therapies are unknown in rare soft tissue sarcomas
such as solitary fibrous tumours (SFTs), whose management in the advanced forms
includes anti-angiogenic therapy. Here, we studied the in situ and systemic
immune status of advanced SFT patients and the effects of sunitinib malate (SM)
in association with the clinical efficacy. METHODS: Immune contexture of SFTs was
assessed by immunohistochemistry in lesions from untreated or SM-treated
patients. Frequency of circulating myeloid-derived suppressor cells (MDSCs),
regulatory T cells (Tregs) and T-cell functions was assessed ex vivo in SFT
patients prior and during anti-angiogenic therapy. Patients with long-term tumour
control were included to correlate immune profiles and clinical responses.
RESULTS: Anti-angiogenic naïve SFT lesions were heavily infiltrated by
CD163(+)CD14(+)CD68(-) and CD163(+)CD14(-)CD68(-) myeloid cells but devoid of T
cells. Conversely, post-SM tumours acquired a new subset of CD68(+)CD14(+)
myeloid cells and displayed traits of an on-going adaptive immunity, strongly
enriched in activated CD8(+) and CD4(+) T cells. These changes at the tumour site
paralleled the alleviation of systemic immunosuppression and the drop in the
frequency of circulating monocytic MDSCs (mMDSCs) and granulocytic MDSCs
(gMDSCs). Rebound in the number of mMDSCs, but not of gMDSCs occurred at disease
progression, and a reduced percentages of mMDSCs, comparable to those found in
healthy donors (HDs), endured only in the SM-responsive patients. CONCLUSIONS:
The immune contexture of SFT patients is heavily involved in anti-angiogenic
therapy and it could be exploited to achieve more durable disease control through
immune-based combination strategies.
|Adaptive Immunity/*drug effects
[MESH]
|Adult
[MESH]
|Aged
[MESH]
|Angiogenesis Inhibitors/*pharmacology/therapeutic use
[MESH]
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