Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes

Amelia Grover, Grace J. Kim, Gregory Lizée, Mary Tschoi, Gang Wang, John R. Wunderlich, Steven A. Rosenberg, Samuel T Hwang, Patrick Hwu

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Purpose: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen - specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. Experimental Design: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. Results: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen - specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. Conclusions: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.

Original languageEnglish (US)
Pages (from-to)5801-5808
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number19
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Fingerprint

Neoplasm Antigens
Dendritic Cells
Vaccination
T-Lymphocytes
Skin
Immunization
Exanthema
Chemokine Receptors
Solar System
Melanoma
Animal Models
MART-1 Antigen
Inflammation
Cancer Vaccines
Antigen Receptors
Cytotoxic T-Lymphocytes
Tumor Burden
Cell Movement
Research Design
Vaccines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Grover, A., Kim, G. J., Lizée, G., Tschoi, M., Wang, G., Wunderlich, J. R., ... Hwu, P. (2006). Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes. Clinical Cancer Research, 12(19), 5801-5808. https://doi.org/10.1158/1078-0432.CCR-05-2421

Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes. / Grover, Amelia; Kim, Grace J.; Lizée, Gregory; Tschoi, Mary; Wang, Gang; Wunderlich, John R.; Rosenberg, Steven A.; Hwang, Samuel T; Hwu, Patrick.

In: Clinical Cancer Research, Vol. 12, No. 19, 01.10.2006, p. 5801-5808.

Research output: Contribution to journalArticle

Grover, A, Kim, GJ, Lizée, G, Tschoi, M, Wang, G, Wunderlich, JR, Rosenberg, SA, Hwang, ST & Hwu, P 2006, 'Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes', Clinical Cancer Research, vol. 12, no. 19, pp. 5801-5808. https://doi.org/10.1158/1078-0432.CCR-05-2421
Grover, Amelia ; Kim, Grace J. ; Lizée, Gregory ; Tschoi, Mary ; Wang, Gang ; Wunderlich, John R. ; Rosenberg, Steven A. ; Hwang, Samuel T ; Hwu, Patrick. / Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 19. pp. 5801-5808.
@article{fd111000805d4416ab2d656c1b35a9e4,
title = "Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes",
abstract = "Purpose: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen - specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. Experimental Design: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. Results: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen - specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. Conclusions: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are {"}imprinted{"} in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.",
author = "Amelia Grover and Kim, {Grace J.} and Gregory Liz{\'e}e and Mary Tschoi and Gang Wang and Wunderlich, {John R.} and Rosenberg, {Steven A.} and Hwang, {Samuel T} and Patrick Hwu",
year = "2006",
month = "10",
day = "1",
doi = "10.1158/1078-0432.CCR-05-2421",
language = "English (US)",
volume = "12",
pages = "5801--5808",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

TY - JOUR

T1 - Intralymphatic dendritic cell vaccination induces tumor antigen - specific, skin-homing T lymphocytes

AU - Grover, Amelia

AU - Kim, Grace J.

AU - Lizée, Gregory

AU - Tschoi, Mary

AU - Wang, Gang

AU - Wunderlich, John R.

AU - Rosenberg, Steven A.

AU - Hwang, Samuel T

AU - Hwu, Patrick

PY - 2006/10/1

Y1 - 2006/10/1

N2 - Purpose: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen - specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. Experimental Design: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. Results: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen - specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. Conclusions: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.

AB - Purpose: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen - specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. Experimental Design: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. Results: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen - specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. Conclusions: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.

UR - http://www.scopus.com/inward/record.url?scp=33750326077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750326077&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-05-2421

DO - 10.1158/1078-0432.CCR-05-2421

M3 - Article

C2 - 17020987

AN - SCOPUS:33750326077

VL - 12

SP - 5801

EP - 5808

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 19

ER -