Abstract
CD2 is a costimulatory protein expressed in all mature T/NK-cells, in particular memory T-cells. CD58 (or LFA-3) is the receptor for CD2 and is ubiquitously expressed. CD2-CD58 interaction has key functions in T-cell activation and organization of the immunological synapse between T- and antigen-presenting cells. Cancer cells have developed multiple mechanisms to evade immune surveillance. Loss of CD58 expression is one frequently reported in diffuse large B-cell lymphomas (DLBCL). On the other hand, in non-hematological neoplasms, tumor infiltrating lymphocytes (TILs) with reduced expression of CD2 have been associated with defective cytotoxicity and T-cell exhaustion. Here, we reported a case of DLBCL involving the jejunal mucosa associated with a rim of cytotoxic reactive T-cells with features of immune evasion (CD2- and TCR-) and T-cell exhaustion (PD1 + high). This case likely exemplifies a previously unrecognized immune evasion mechanism in lymphoma involving a decreased CD2 expression in the lymphoma-associated T-cells.
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References
Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla-Favera R (2011) Combined genetic inactivation of beta2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 20:728–740. https://doi.org/10.1016/j.ccr.2011.11.006
Demetriou P, Abu-Shah E, Valvo S, McCuaig S, Mayya V, Kvalvaag A, Starkey T, Korobchevskaya K, Lee LYW, Friedrich M, Mann E, Kutuzov MA, Morotti M, Wietek N, Rada H, Yusuf S, Afrose J, Siokis A, Oxford IBDCI, Meyer-Hermann M, Ahmed AA, Depoil D, Dustin ML (2020) A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals. Nat Immunol 21:1232–1243. https://doi.org/10.1038/s41590-020-0770-x
Demetriou P, Abu-Shah E, Valvo S, McCuaig S, Mayya V, Kvalvaag A, Starkey T, Korobchevskaya K, Lee LYW, Friedrich M, Mann E, Kutuzov MA, Morotti M, Wietek N, Rada H, Yusuf S, Afrose J, Siokis A, Oxford IBDCI, Meyer-Hermann M, Ahmed AA, Depoil D, Dustin ML (2021) Author correction: a dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals. Nat Immunol 22:99. https://doi.org/10.1038/s41590-020-00825-w
Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS (1998) A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell 94:667–677. https://doi.org/10.1016/s0092-8674(00)81608-6
Koneru M, Monu N, Schaer D, Barletta J, Frey AB (2006) Defective adhesion in tumor infiltrating CD8+ T cells. J Immunol 176:6103–6111. https://doi.org/10.4049/jimmunol.176.10.6103
McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KG (2015) T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 523:612–616. https://doi.org/10.1038/nature14468
Menter T, Tzankov A (2018) Mechanisms of immune evasion and immune modulation by lymphoma cells. Front Oncol 8:54. https://doi.org/10.3389/fonc.2018.00054
Otsuka Y, Nishikori M, Arima H, Izumi K, Kitawaki T, Hishizawa M, Takaori-Kondo A (2020) EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas. Mol Immunol 119:35–45. https://doi.org/10.1016/j.molimm.2020.01.006
Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, Carpenter Z, Abate F, Allegretta M, Haydu JE, Jiang X, Lossos IS, Nicolas C, Balbin M, Bastard C, Bhagat G, Piris MA, Campo E, Bernard OA, Rabadan R, Ferrando AA (2014) Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet 46:166–170. https://doi.org/10.1038/ng.2873
Sanchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff SJ, Springer TA (1982) Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A 79:7489–7493. https://doi.org/10.1073/pnas.79.23.7489
Siokis A, Robert PA, Demetriou P, Dustin ML, Meyer-Hermann M (2018) F-actin-driven CD28-CD80 localization in the immune synapse. Cell Rep 24:1151–1162. https://doi.org/10.1016/j.celrep.2018.06.114
Acknowledgements
This study was supported by the Translational Molecular Pathology-Immunoprofiling laboratory (TMP-IL) at the Department Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center.
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AG, XW, TGS, JC, and JM contributed reviewing the slides, summarizing the clinical and pathology data, and drafting the manuscript. ML M-P and FV reviewed and wrote the final version of the manuscript. KK, WL, and LS performed IHC studies; JC and GT performed and analyzed the FISH studies.
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Ghosh, A., Marques-Piubelli, M.L., Wang, X. et al. CD2-negative lymphoma-associated T-cells: a potential mechanism of immune-evasion in diffuse large B-cell lymphoma. Virchows Arch 481, 659–663 (2022). https://doi.org/10.1007/s00428-022-03348-x
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DOI: https://doi.org/10.1007/s00428-022-03348-x