TY - JOUR

T1 - Malignant inflammation in cutaneous T-cell lymphoma—a hostile takeover

AU - Krejsgaard, Thorbjørn

AU - Lindahl, Lise M.

AU - Mongan, Nigel P.

AU - Wasik, Mariusz A.

AU - Litvinov, Ivan V.

AU - Iversen, Lars

AU - Langhoff, Erik

AU - Woetmann, Anders

AU - Odum, Niels

PY - 2017

Y1 - 2017

N2 - Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term “malignant inflammation” as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL.

AB - Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term “malignant inflammation” as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL.

KW - Cancer

KW - Cutaneous T-cell lymphoma

KW - Infection

KW - Inflammation

KW - Malignant T cells

KW - Pathogenesis

U2 - 10.1007/s00281-016-0594-9

DO - 10.1007/s00281-016-0594-9

M3 - Review

C2 - 27717961

AN - SCOPUS:84990996507

VL - 39

SP - 269

EP - 282

JO - Seminars in Immunopathology

JF - Seminars in Immunopathology

SN - 1863-2297

IS - 3

ER -