upon T‐cell activation, MYC controls lactate transporter expression, regulating the feedback on glycolytic flux fueling T‐cell synthetic programs and proliferative attitude [19]. In PTCL‐NOS not otherwise specified, overexpression of MYC and its transcriptional targets involved in cell proliferation has been implicated in the worse prognosis of GATA3‐positive cases [20]. Nevertheless, in the light of the profound effects on the metabolic adaptation to TCR sensing, MYC may represent an underrated determinant of inter/intraclonal competition [21] underlying PTCL progression.
Figure 1.3 The biomass of CD8+ effector T cells is dramatically different between peritumoral (left panel) and intratumoral (right panel) compartments of a high‐grade carcinoma. Intra‐tumoral CD8+ effectors corresponding to an activated state showing a larger size.
Source: Claudio Tripodo, Stefano Pilleri.
This introductory chapter provides an updated view of the mature T‐cell constellation, in a less static view, as compared with canonical ontogeny‐focused outlines, providing information on the biological foundations of functional plasticity, phenotypical heterogeneity, and transcriptional dynamics that are recapitulated and magnified in peripheral T‐cell malignancies. It is imperative to recognize that the diversity, and complex function of normal T cells, is central to appreciating the many histologic and genetic subtypes of PTCL, and may aid in explaining the diverse behavior and presentation of these challenging and heterogeneous diseases.
Must Reads
Litman, G.W., Cannon, J.P., and Dinshaw, L.J.. (2005). Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol 5(11): 866–879.
Restifo, N.P. and Gattinoni, L. (2013). Lineage relationship of effector and memory T‐cell. Curr Opin Immunol 25(5): 556–563.
Withers, D.R. (2016). Innate lymphoid cells regulation of adaptive immunity. Immunology 149(2): 123–130.
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2 Mechanisms of T‐cell Lymphomagenesis
François Lemonnier1,2,3, Philippe Gaulard2,3,4 and Laurence de Leval5
1 Unité hémopathies Lymphoïdes, Hôpitaux Universitaires Henri Mondor, Créteil, France
2 Assistance Publique des Hôpitaux de Paris, Paris, France
3 Institut Mondor de Recherche Biomédicale, INSERMU955, Université Paris Est Créteil, Créteil, France
4 Département de Pathologie, Hôpitaux Universitaires Henri Mondor, Créteil, France
5 Institut de Pathologie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
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