Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma

Lise M Lindahl; Andreas Willerslev-Olsen; Lise M R Gjerdrum; Pia R Nielsen; Edda Blümel; Anne H Rittig; Pamela Celis; Bjorn Herpers; Jürgen C Becker; Birgitte Stausbøl-Grøn; Mariusz A Wasik; Maria Gluud; Simon Fredholm; Terkild B Buus; Claus Johansen; Claudia Nastasi; Lukas Peiffer; Linda Kubat; Michael Bzorek; Jens O Eriksen; Thorbjørn Krejsgaard; Charlotte M Bonefeld; Carsten Geisler; Tomas Mustelin; Erik Langhoff; Michael Givskov; Anders Woetmann; Mogens Kilian; Thomas Litman; Lars Iversen; Niels Odum

doi:10.1182/blood.2018888107

Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma

Lise M Lindahl, Andreas Willerslev-Olsen, Lise M R Gjerdrum, Pia R Nielsen, Edda Blümel, Anne H Rittig, Pamela Celis, Bjorn Herpers, Jürgen C Becker, Birgitte Stausbøl-Grøn, Mariusz A Wasik, Maria Gluud, Simon Fredholm, Terkild B Buus, Claus Johansen, Claudia Nastasi, Lukas Peiffer, Linda Kubat, Michael Bzorek, Jens O EriksenThorbjørn Krejsgaard, Charlotte M Bonefeld, Carsten Geisler, Tomas Mustelin, Erik Langhoff, Michael Givskov, Anders Woetmann, Mogens Kilian, Thomas Litman, Lars Iversen, Niels Odum

41 Citations (Scopus)

Abstract

It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.

Original language	English
Journal	Blood
Volume	134
Issue number	13
Pages (from-to)	1072-1083
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood.2018888107
Publication status	Published - 26 Sept 2019

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Lindahl, L. M., Willerslev-Olsen, A., Gjerdrum, L. M. R., Nielsen, P. R., Blümel, E., Rittig, A. H., Celis, P., Herpers, B., Becker, J. C., Stausbøl-Grøn, B., Wasik, M. A., Gluud, M., Fredholm, S., Buus, T. B., Johansen, C., Nastasi, C., Peiffer, L., Kubat, L., Bzorek, M., ... Odum, N. (2019). Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma. Blood, 134(13), 1072-1083. https://doi.org/10.1182/blood.2018888107

Lindahl, LM, Willerslev-Olsen, A, Gjerdrum, LMR, Nielsen, PR, Blümel, E, Rittig, AH, Celis, P, Herpers, B, Becker, JC, Stausbøl-Grøn, B, Wasik, MA, Gluud, M, Fredholm, S, Buus, TB, Johansen, C, Nastasi, C, Peiffer, L, Kubat, L, Bzorek, M, Eriksen, JO, Krejsgaard, T, Bonefeld, CM, Geisler, C, Mustelin, T, Langhoff, E, Givskov, M , Woetmann, A, Kilian, M, Litman, T, Iversen, L & Odum, N 2019, 'Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma', Blood, vol. 134, no. 13, pp. 1072-1083. https://doi.org/10.1182/blood.2018888107

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title = "Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma",

abstract = "It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.",

author = "Lindahl, {Lise M} and Andreas Willerslev-Olsen and Gjerdrum, {Lise M R} and Nielsen, {Pia R} and Edda Bl{\"u}mel and Rittig, {Anne H} and Pamela Celis and Bjorn Herpers and Becker, {J{\"u}rgen C} and Birgitte Stausb{\o}l-Gr{\o}n and Wasik, {Mariusz A} and Maria Gluud and Simon Fredholm and Buus, {Terkild B} and Claus Johansen and Claudia Nastasi and Lukas Peiffer and Linda Kubat and Michael Bzorek and Eriksen, {Jens O} and Thorbj{\o}rn Krejsgaard and Bonefeld, {Charlotte M} and Carsten Geisler and Tomas Mustelin and Erik Langhoff and Michael Givskov and Anders Woetmann and Mogens Kilian and Thomas Litman and Lars Iversen and Niels Odum",

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doi = "10.1182/blood.2018888107",

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T1 - Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma

AU - Lindahl, Lise M

AU - Willerslev-Olsen, Andreas

AU - Gjerdrum, Lise M R

AU - Nielsen, Pia R

AU - Blümel, Edda

AU - Rittig, Anne H

AU - Celis, Pamela

AU - Herpers, Bjorn

AU - Becker, Jürgen C

AU - Stausbøl-Grøn, Birgitte

AU - Wasik, Mariusz A

AU - Gluud, Maria

AU - Fredholm, Simon

AU - Buus, Terkild B

AU - Johansen, Claus

AU - Nastasi, Claudia

AU - Peiffer, Lukas

AU - Kubat, Linda

AU - Bzorek, Michael

AU - Eriksen, Jens O

AU - Krejsgaard, Thorbjørn

AU - Bonefeld, Charlotte M

AU - Geisler, Carsten

AU - Mustelin, Tomas

AU - Langhoff, Erik

AU - Givskov, Michael

AU - Woetmann, Anders

AU - Kilian, Mogens

AU - Litman, Thomas

AU - Iversen, Lars

AU - Odum, Niels

PY - 2019/9/26

Y1 - 2019/9/26

N2 - It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.

AB - It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.

U2 - 10.1182/blood.2018888107

DO - 10.1182/blood.2018888107

M3 - Journal article

C2 - 31331920

SN - 0006-4971

VL - 134

SP - 1072

EP - 1083

JO - Blood

JF - Blood

IS - 13

ER -

Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma

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