Casey Means1,2, Daniel R Clayburgh2,3,4,5, Lauren Maloney1, David Sauer6, Matthew H Taylor3,4, Maisie L Shindo2, Lisa M Coussens1,4, Takahiro Tsujikawa1,2,7. 1. Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, Oregon. 2. Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon. 3. Department of Hematology and Medical Oncology, Oregon Health and Science University, Portland, Oregon. 4. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon. 5. Operative Care Division, Portland Veterans' Affairs Health Care System, Portland, Oregon. 6. Department of Pathology, Oregon Health and Science University, Portland, Oregon. 7. Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Abstract
BACKGROUND: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. METHODS: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. RESULTS: mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8+ T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. CONCLUSIONS: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.
BACKGROUND:Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. METHODS: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAFV600E mutational status. RESULTS:mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8+ T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. CONCLUSIONS: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.
Authors: Grace Banik; Courtney B Betts; Shannon M Liudahl; Shamilene Sivagnanam; Rie Kawashima; Tiziana Cotechini; William Larson; Jeremy Goecks; Sara I Pai; Daniel R Clayburgh; Takahiro Tsujikawa; Lisa M Coussens Journal: Methods Enzymol Date: 2019-07-02 Impact factor: 1.600
Authors: Martina Sollini; Luca di Tommaso; Margarita Kirienko; Chiara Piombo; Marco Erreni; Andrea Gerardo Lania; Paola Anna Erba; Lidija Antunovic; Arturo Chiti Journal: EJNMMI Res Date: 2019-10-15 Impact factor: 3.138