TY - JOUR
T1 - Sting Is Commonly and Differentially Expressed in T-and Nk-Cell but Not B-Cell Non-Hodgkin Lymphomas
AU - Xagoraris, Ioanna
AU - Farrajota Neves da Silva, Pedro
AU - Kokaraki, Georgia
AU - Stathopoulou, Konstantina
AU - Wahlin, Björn
AU - Österborg, Anders
AU - Herold, Nikolas
AU - Ng, Siok Bian
AU - Medeiros, L. Jeffrey
AU - Drakos, Elias
AU - Sander, Birgitta
AU - Rassidakis, George Z.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - The expression patterns of stimulator of interferon genes (STING) were investigated in a cohort of 158 T-and natural killer (NK)-cell and 265 B-cell non-Hodgkin lymphomas (NHLs), as well as in control reactive lymph nodes and tonsils. STING expression was assessed by immunohistochemical methods using diagnostic biopsy specimens obtained prior to treatment. Using an arbitrary 10% cutoff, STING was differentially expressed among T/NK-cell NHLs; positive in 36 out of 38 (95%) cases of ALK+ anaplastic large cell lymphoma (ALCL), 23 out of 37 (62%) ALK-ALCLs, 1 out of 13 (7.7%) angioimmunoblastic T-cell lymphomas, 15 out of 19 (79%) peripheral T-cell lymphomas, not otherwise specified, 20 out of 36 (56%) extranodal NK/T-cell lymphomas of nasal type, 6 out of 7 (86%) T-cell lymphoblastic lymphomas, and 3 out of 4 (75%) mycosis fungoides. STING expression did not correlate with clinicopathological parameters or outcome in these patients with T/NK-cell lymphoma. By contrast, all 265 B-cell NHLs of various types were STING-negative. In addition, STING mRNA levels were very high in 6 out of 7 T-cell NHL cell lines, namely, ALK+ and ALK-ALCL cell lines, and very low or undetectable in 7 B-cell NHL cell lines, suggesting transcriptional downregulation of STING in neoplastic B-cells. At the protein level, using Western blot analysis and immunohistochemistry performed on cell blocks, STING expression was found to be restricted to T-cell NHL cell lines. Taken together, STING expression represents a novel biomarker and therapeutic target in T-and NK-cell lymphomas with direct immunotherapeutic implications since modulators of cGAS–STING activity are already available for clinical use.
AB - The expression patterns of stimulator of interferon genes (STING) were investigated in a cohort of 158 T-and natural killer (NK)-cell and 265 B-cell non-Hodgkin lymphomas (NHLs), as well as in control reactive lymph nodes and tonsils. STING expression was assessed by immunohistochemical methods using diagnostic biopsy specimens obtained prior to treatment. Using an arbitrary 10% cutoff, STING was differentially expressed among T/NK-cell NHLs; positive in 36 out of 38 (95%) cases of ALK+ anaplastic large cell lymphoma (ALCL), 23 out of 37 (62%) ALK-ALCLs, 1 out of 13 (7.7%) angioimmunoblastic T-cell lymphomas, 15 out of 19 (79%) peripheral T-cell lymphomas, not otherwise specified, 20 out of 36 (56%) extranodal NK/T-cell lymphomas of nasal type, 6 out of 7 (86%) T-cell lymphoblastic lymphomas, and 3 out of 4 (75%) mycosis fungoides. STING expression did not correlate with clinicopathological parameters or outcome in these patients with T/NK-cell lymphoma. By contrast, all 265 B-cell NHLs of various types were STING-negative. In addition, STING mRNA levels were very high in 6 out of 7 T-cell NHL cell lines, namely, ALK+ and ALK-ALCL cell lines, and very low or undetectable in 7 B-cell NHL cell lines, suggesting transcriptional downregulation of STING in neoplastic B-cells. At the protein level, using Western blot analysis and immunohistochemistry performed on cell blocks, STING expression was found to be restricted to T-cell NHL cell lines. Taken together, STING expression represents a novel biomarker and therapeutic target in T-and NK-cell lymphomas with direct immunotherapeutic implications since modulators of cGAS–STING activity are already available for clinical use.
KW - Immune response
KW - STING
KW - T-cell non-Hodgkin lymphoma
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U2 - 10.3390/cancers14051186
DO - 10.3390/cancers14051186
M3 - Article
C2 - 35267494
AN - SCOPUS:85125179694
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 5
M1 - 1186
ER -