Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

D. Schrama; H. Voigt; A.O. Eggert; R. Xiang; H. Zhou; T.N. Schumacher; M.H. Andersen; Straten P. thor; R.A. Reisfeld; J.C. Becker

doi:10.1007/s00262-007-0352-x

Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

D. Schrama, H. Voigt, A.O. Eggert, R. Xiang, H. Zhou, T.N. Schumacher, M.H. Andersen, Straten P. thor, R.A. Reisfeld, J.C. Becker

32 Citationer (Scopus)

Abstract

BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells as demonstrated by in situ TRP-2/K(b) tetramer staining. Mechanistically, targeted LTalpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. CONCLUSION: Thus, our data demonstrate that targeted LTalpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site
Udgivelsesdato: 2008/1

Originalsprog	Engelsk
Tidsskrift	Cancer Immunology, Immunotherapy
Vol/bind	57
Udgave nummer	1
Sider (fra-til)	85-95
Antal sider	10
ISSN	0340-7004
DOI	https://doi.org/10.1007/s00262-007-0352-x
Status	Udgivet - 2008

Adgang til dokumentet

10.1007/s00262-007-0352-x

Citationsformater

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title = "Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue",

abstract = "BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells as demonstrated by in situ TRP-2/K(b) tetramer staining. Mechanistically, targeted LTalpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. CONCLUSION: Thus, our data demonstrate that targeted LTalpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site Udgivelsesdato: 2008/1",

author = "D. Schrama and H. Voigt and A.O. Eggert and R. Xiang and H. Zhou and T.N. Schumacher and M.H. Andersen and thor, {Straten P.} and R.A. Reisfeld and J.C. Becker",

year = "2008",

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T1 - Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

AU - Schrama, D.

AU - Voigt, H.

AU - Eggert, A.O.

AU - Xiang, R.

AU - Zhou, H.

AU - Schumacher, T.N.

AU - Andersen, M.H.

AU - thor, Straten P.

AU - Reisfeld, R.A.

AU - Becker, J.C.

PY - 2008

Y1 - 2008

N2 - BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells as demonstrated by in situ TRP-2/K(b) tetramer staining. Mechanistically, targeted LTalpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. CONCLUSION: Thus, our data demonstrate that targeted LTalpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site Udgivelsesdato: 2008/1

AB - BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells as demonstrated by in situ TRP-2/K(b) tetramer staining. Mechanistically, targeted LTalpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. CONCLUSION: Thus, our data demonstrate that targeted LTalpha promotes an accelerated immune response by enabling the priming of T cells at the tumor site Udgivelsesdato: 2008/1

U2 - 10.1007/s00262-007-0352-x

DO - 10.1007/s00262-007-0352-x

M3 - Journal article

C2 - 17605009

SN - 0340-7004

VL - 57

SP - 85

EP - 95

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

IS - 1

ER -