scholarly journals 752 The impact of grade of differentiation and BRAF mutation status on neoantigen and immune landscape in papillary thyroid cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A800-A800
Author(s):  
Myungwoo Nam ◽  
Myungwoo Nam ◽  
Woojung Yang ◽  
Ju Young Lee ◽  
Jaeyoun Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Braf Mutation ◽  
Cytolytic Activity ◽  
Activity Score ◽  
Cyt B ◽  
Mutation Status ◽  
Poorly Differentiated ◽  
Immune Traits ◽  
Well Differentiated

BackgroundThe use of immune checkpoint inhibitors (ICIs) in cancer treatment has been approved by the FDA, but its application is experimental in the treatment of papillary thyroid cancer (PTC). Induction of immune response via recognition of neoantigens is considered to be the basis for the treatment mechanism of ICIs.1 However, the neoantigen landscape has not been explored in PTC. Our aim is to investigate the immune landscape of PTC in relation to neoantigens, taking into account the BRAF mutation status and grade of differentiation as contributing factors.MethodsBRAF V600E mutation status and thyroid differentiation scores (TDSs) were gathered from the PTC cohort of The Cancer Genome Atlas (TCGA). TDS was derived from the mRNA expression levels of 16 thyroid function genes to quantify the grade of differentiation. Tumors with TDSs in the 1st quartile and 4th quartile were defined as poorly differentiated and well differentiated, respectively. The neoantigen burden for each sample was predicted using CloudNeo pipeline. The infiltration of immune cells was calculated through CIBERSORT.ResultsAmong 400 patients with predicted neoantigen data, 187 (47%) had BRAF mutations. The BRAF mutated tumors showed increased cytolytic activity score (CYT, p=0.001), increased infiltration of regulatory T cells (Treg, p<0.001), and higher PD-L1 expression (p<0.001) compared to BRAF wild-type tumors (figure 1). In regard to grade of differentiation, poorly differentiated tumors showed increased CYT (p=0.002), increased infiltration of Treg (p<0.001), and higher PD-L1 expression (p<0.001) compared to well differentiated tumors (figure 2). However, BRAF mutation status or grade of differentiation did not correlate with the neoantigen burden. Also, the neoantigen burden did not show any correlations with immune landscape features such as infiltration of CD8+ T cells or Treg, CYT, and PD-L1 expression.Abstract 752 Figure 1Immune traits according to BRAF mutation status. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.Abstract 752 Figure 2Immune traits according to grade of differentiation. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.ConclusionsIncreased CYT and higher expression of PD-L1 in the BRAF mutated or the poorly differentiated tumors imply the possible role of ICI use in these subgroups of patients. However, the immune response to these subgroups does not seem to be mediated through the increase in neoantigen formation. Further studies are warranted to explore markers for immunotherapy implication.ReferencesSchumacher TN, Schreiber RD, Neoantigens in cancer immunotherapy. Science 2015; 348:69–74.

Immunofluorescence-Detected Infiltration of CD4+FOXP3+ Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer

2011 ◽  
Vol 21 (9) ◽  
pp. 1628-1634 ◽  
Author(s):  
Wataru Yamagami ◽  
Nobuyuki Susumu ◽  
Hideo Tanaka ◽  
Akira Hirasawa ◽  
Kouji Banno ◽  
...  
Keyword(s):  
T Cells ◽  
Endometrial Cancer ◽  
Regulatory T Cells ◽  
Clinicopathological Factors ◽  
Early Stage Disease ◽  
Cell Counts ◽  
Stage Disease ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Lymphovascular Space Invasion

ObjectiveHost antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8+ cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.MethodsThe study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4+FOXP3+ cells were identified as Tregs in this study. The numbers of CD8+ cells, CD4+ cells, and Tregs as well as the Treg/CD8+ and Treg/CD4+ ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.ResultsOf the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8+ and CD4+ cell counts, Treg count, and Treg/CD8+ and Treg/CD4+ ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8+ ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8+ ratios (P < 0.05).ConclusionsThe Treg count and Treg/CD8+ ratio may be new prognostic factors for endometrial cancer.

Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Autoimmunity ◽  
2009 ◽  
pp. 1-1
Author(s):  
Jose Miguel Sempere-Ortells ◽  
Vicente Perez-Garcia ◽  
Gema Marin-Alberca ◽  
Alejandra Peris-Pertusa ◽  
Jose Miguel Benito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score

scholarly journals THE ROLE OF BRAF MUTATION STATUS IN SURGICAL TREATMENT OF WELL-DIFFERENTIATED THYROID CANCER

2016 ◽  
Vol 6 (4) ◽  
pp. 45-48
Author(s):  
A. P. Polyakov ◽  
N. N. Volchenko ◽  
E. N. Slavnova ◽  
A. V. Kudryavtseva ◽  
M. V. Ratushnyy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Surgical Treatment ◽  
Braf Mutation ◽  
Differentiated Thyroid Cancer ◽  
Mutation Status ◽  
Well Differentiated

Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Autoimmunity ◽  
2009 ◽  
Vol 42 (8) ◽  
pp. 636-645 ◽  
Author(s):  
José Miguel Sempere-Ortells ◽  
Vicente Pérez-García ◽  
Gema Marín-Alberca ◽  
Alejandra Peris-Pertusa ◽  
José Miguel Benito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score

Motility of leukemic lymphocytes

1990 ◽  
Vol 48 (3) ◽  
pp. 368-369
Author(s):  
Manoj Raje ◽  
Karvita B. Ahluwalia
Keyword(s):  
Quantitative Data ◽  
Laser Doppler Velocimetry ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Cellular Space ◽  
Differentiated Cells ◽  
Poorly Differentiated ◽  
Solid Tissues ◽  
Well Differentiated ◽  
Reduced Mobility

In Acute Lymphocytic Leukemia motility of lymphocytes is associated with dissemination of malignancy and establishment of metastatic foci. Normal and leukemic lymphocytes in circulation reach solid tissues where due to in adequate perfusion some cells get trapped among tissue spaces. Although normal lymphocytes reenter into circulation leukemic lymphocytes are thought to remain entrapped owing to reduced mobility and form secondary metastasis. Cell surface, transmembrane interactions, cytoskeleton and level of cell differentiation are implicated in lymphocyte mobility. An attempt has been made to correlate ultrastructural information with quantitative data obtained by Laser Doppler Velocimetry (LDV). TEM of normal & leukemic lymphocytes revealed heterogeneity in cell populations ranging from well differentiated (Fig. 1) to poorly differentiated cells (Fig. 2). Unlike other cells, surface extensions in differentiated lymphocytes appear to originate by extrusion of large vesicles in to extra cellular space (Fig. 3). This results in persistent unevenness on lymphocyte surface which occurs due to a phenomenon different from that producing surface extensions in other cells.

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