23 research outputs found

    Circulating immunophenotypes are potentially prognostic in follicular cell-derived thyroid cancer

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    BackgroundExploring the immune interface of follicular cell-derived thyroid cancer has prognostic and therapeutic potential. The available literature is lacking for comprehensive immunophenotyping in relation to clinical outcomes. In this study, we identify circulating immunophenotypes associated with thyroid cancer prognosis.MethodsWe conducted a pilot observational study of adults with follicular cell-derived thyroid cancer who underwent surgery at our tertiary care referral center and had consented for flow cytometry on peripheral blood collected at the time of thyroidectomy.ResultsOf the 32 included subjects, 20 (62%) had well differentiated, 5 (16%) had poorly differentiated, and 7 (22%) had anaplastic thyroid cancer. The most frequent AJCC stage was 4 (59%) and the ATA risk of recurrence category was high (56%). Patients with AJCC stage 3/4 demonstrated fewer circulating mononuclear cells (CD45+), more monocytes (CD14+), fewer total lymphocytes (CD14-), fewer T cells (CD3+), fewer CD4+ T cells, fewer gamma-delta T cells, fewer natural killer (NK) T-like cells, more myeloid-derived suppressor cells (MDSCs; Lin-CD33+HLADR-), and more effector memory T cells but similar CD8+ T cells compared to stage1/2. Immunophenotype comparisons by ATA risk stratification and course of thyroid cancer were comparable to those observed for stage, except for significant differences in memory T cell subtypes. The median follow-up was 58 months.ConclusionsAggressive follicular cell-derived thyroid cancer either at presentation or during follow-up is associated with down-regulation of the T cell populations specifically CD4+ T cells, gamma-delta T cells, and NK T-like cells but up-regulation of MDSCs and altered memory T cells. These immunophenotypes are potential prognostic biomarkers supporting future investigation for developing targeted immunotherapies against advanced thyroid cancer

    Alien Registration- Ryder, Mabel (Waterville, Kennebec County)

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    https://digitalmaine.com/alien_docs/14570/thumbnail.jp

    Alien Registration- Ryder, Mabel (Waterville, Kennebec County)

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    https://digitalmaine.com/alien_docs/14570/thumbnail.jp

    Genetic and pharmacological targeting of CSF-1/CSF-1R inhibits tumor-associated macrophages and impairs BRAF-induced thyroid cancer progression.

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    Advanced human thyroid cancers are densely infiltrated with tumor-associated macrophages (TAMs) and this correlates with a poor prognosis. We used BRAF-induced papillary thyroid cancer (PTC) mouse models to examine the role of TAMs in PTC progression. Following conditional activation of BRAF(V600E) in murine thyroids there is an increased expression of the TAM chemoattractants Csf-1 and Ccl-2. This is followed by the development of PTCs that are densely infiltrated with TAMs that express Csf-1r and Ccr2. Targeting CCR2-expressing cells during BRAF-induction reduced TAM density and impaired PTC development. This strategy also induced smaller tumors, decreased proliferation and restored a thyroid follicular architecture in established PTCs. In PTCs from mice that lacked CSF-1 or that received a c-FMS/CSF-1R kinase inhibitor, TAM recruitment and PTC progression was impaired, recapitulating the effects of targeting CCR2-expressing cells. Our data demonstrate that TAMs are pro-tumorigenic in advanced PTCs and that they can be targeted pharmacologically, which may be potentially useful for patients with advanced thyroid cancers

    TAMs and CAFs densely infiltrate thyroid tissue during BRAF-induced PTC initiation.

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    <p>FACS analysis of thyroid tissue from T<i>g-rtTA/tetO-BRAF<sup>V600E</sup></i> mice, in the absence (A) or presence of dox (B–E). A, Wild type thyroids have a low abundance of resident tissue Mø as measured by anti-F4/80. Seven days after dox, ∼50% of cells are Cd45<sup>+</sup> leukocytes (B), that are F4/80+ and Cd11b+ (C–D). Most TAMs co-express F4/80 and Cd11b (E). FACS analyses were done on pooled wild type (no dox: n = 6) and dox-induced (n = 4) thyroids. F) IHC stain of representative frozen section of dox-induced thyroid tissue with anti-Cd68<sup>+</sup> (red stain) and DAPI (blue) showing dense staining of TAMs around thyroid follicular cell nests (asterix). G) IHC with anti-αSMA+ (brown stain) demonstrates strong staining (arrows) between nests of cancer cells (asterix). H) Immunofluorescent staining with vimentin (green) is similar to that of αSMA (G, I), consistent with a dense CAF stromal compartment. I) Dual label immunofluorescence with anti-Cd11b (red) and anti-αSMA (green) did not demonstrate co-localization, consistent with the presence of two different cell types (TAMs and CAFs, respectively). F, H) Sections were co-stained with DAPI (F,H: 20× magnification; G: 10× magnification).</p

    The c-FMS/CSF-1R kinase inhibitor GW2580 decreases tumor macrophages and impairs Braf-induced thyroid cancer development.

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    <p>A–D) Representative thyroid sections for the indicated stains from 7 day dox-induced <i>Tg-rtTA/tetO-Braf</i> mice treated with either vehicle (n = 4) or GW2580-impregnated chow (n = 4): A) H/E; B) Iba-1; C) αSMA; D)Ki67. E) Thyroid weights of dox-induced, vehicle vs. GW2580-treated mice (*p = 0.02). F) Quantification for the indicated stains; * p<0.001, ** p<0.01.</p
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