Evidence for oligoclonal T-cell response in a metastasis of renal cell carcinoma responding to vaccination with autologous tumor cells and transfer of in vitro-sensitized vaccine-draining lymph node lymphocytes

Eckhart Weidmann, Theodore Logan, Satoshi Yasumura, John M. Kirkwood, Massimo Trucco, Theresa L. Whiteside

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) of a patient with von Hippel-Lindau disease and renal cell carcinoma were studied for the T-cell receptor β chain variable region (TCR-Vβ) repertoire. The patient was vaccinated with irradiated autologous tumor cells from a renal tumor mass, a vaccine-draining lymph node was removed, and lymphocytes were cultured in the presence of autologous tumor cells and low-dose interleukin 2 (IL2). These lymphocytes were adoptively transferred to the patient together with systemic IL2 (30,000 ID/kg every 8 h). Analysis of TCR-Vβ expression was performed by polymerase chain reaction in PBL before, during, and after therapy, in vaccine-draining lymph node lymphocytes, and in TIL obtained from moderately infiltrated, nonresponding renal tumor mass and from a more intensely infiltrated lung metastasis, which was responding to treatment. Significant differences in the expression of TCR-Vβ13.1 by T-cells recovered from these various sites were observed. Also, TIL recovered from the responding lung metastasis and cultured in the presence of IL2 gave rise to autologous tumor-reactive CD4+ T-cells, whereas the nonresponsive renal tumor yielded a mixture of T- and natural killer cells. In PBL obtained prior to treatment and during IL2 therapy, expression of Vβ13.1 was 0.7 and 1.8%, respectively, of the total Vβ gene repertoire. Fresh vaccine-draining lymph node lymphocytes contained 5.9% of Vβ13.1-expressing T-cells. After IL2 therapy, Vβ13.1 gene expression increased to 5.4% in PBL. In the nonresponding tumor mass, the frequency of Vβ13.1 gene expression among TIL was 12%, whereas in the responding, highly infiltrated nodule, it was 28%, with a striking loss of expression of other Vβ gene families. Sequencing of the amplified product of Vβ13.1 complementary DNA from the responding pulmonary metastasis showed restrictions in the complementarity-determining region 3. Thus, in vivo expansion of Vβ13.1-expressing CD4+ T-cells, possibly in response to a tumorassociated antigen, occurred in the responding tumor mass following this form of therapy and correlated with tumor course.

Original languageEnglish (US)
Pages (from-to)4745-4749
Number of pages5
JournalCancer Research
Volume53
Issue number20
StatePublished - Oct 15 1993
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Vaccination
Vaccines
Lymph Nodes
Lymphocytes
Neoplasm Metastasis
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Interleukin-2
Neoplasms
T-Cell Antigen Receptor
Kidney
Lung
Complementarity Determining Regions
von Hippel-Lindau Disease
Therapeutics
Gene Expression
In Vitro Techniques
Active Immunotherapy
Natural Killer T-Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evidence for oligoclonal T-cell response in a metastasis of renal cell carcinoma responding to vaccination with autologous tumor cells and transfer of in vitro-sensitized vaccine-draining lymph node lymphocytes. / Weidmann, Eckhart; Logan, Theodore; Yasumura, Satoshi; Kirkwood, John M.; Trucco, Massimo; Whiteside, Theresa L.

In: Cancer Research, Vol. 53, No. 20, 15.10.1993, p. 4745-4749.

Research output: Contribution to journalArticle

@article{f4439492f2194494bb860441babf0a23,
title = "Evidence for oligoclonal T-cell response in a metastasis of renal cell carcinoma responding to vaccination with autologous tumor cells and transfer of in vitro-sensitized vaccine-draining lymph node lymphocytes",
abstract = "Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) of a patient with von Hippel-Lindau disease and renal cell carcinoma were studied for the T-cell receptor β chain variable region (TCR-Vβ) repertoire. The patient was vaccinated with irradiated autologous tumor cells from a renal tumor mass, a vaccine-draining lymph node was removed, and lymphocytes were cultured in the presence of autologous tumor cells and low-dose interleukin 2 (IL2). These lymphocytes were adoptively transferred to the patient together with systemic IL2 (30,000 ID/kg every 8 h). Analysis of TCR-Vβ expression was performed by polymerase chain reaction in PBL before, during, and after therapy, in vaccine-draining lymph node lymphocytes, and in TIL obtained from moderately infiltrated, nonresponding renal tumor mass and from a more intensely infiltrated lung metastasis, which was responding to treatment. Significant differences in the expression of TCR-Vβ13.1 by T-cells recovered from these various sites were observed. Also, TIL recovered from the responding lung metastasis and cultured in the presence of IL2 gave rise to autologous tumor-reactive CD4+ T-cells, whereas the nonresponsive renal tumor yielded a mixture of T- and natural killer cells. In PBL obtained prior to treatment and during IL2 therapy, expression of Vβ13.1 was 0.7 and 1.8{\%}, respectively, of the total Vβ gene repertoire. Fresh vaccine-draining lymph node lymphocytes contained 5.9{\%} of Vβ13.1-expressing T-cells. After IL2 therapy, Vβ13.1 gene expression increased to 5.4{\%} in PBL. In the nonresponding tumor mass, the frequency of Vβ13.1 gene expression among TIL was 12{\%}, whereas in the responding, highly infiltrated nodule, it was 28{\%}, with a striking loss of expression of other Vβ gene families. Sequencing of the amplified product of Vβ13.1 complementary DNA from the responding pulmonary metastasis showed restrictions in the complementarity-determining region 3. Thus, in vivo expansion of Vβ13.1-expressing CD4+ T-cells, possibly in response to a tumorassociated antigen, occurred in the responding tumor mass following this form of therapy and correlated with tumor course.",
author = "Eckhart Weidmann and Theodore Logan and Satoshi Yasumura and Kirkwood, {John M.} and Massimo Trucco and Whiteside, {Theresa L.}",
year = "1993",
month = "10",
day = "15",
language = "English (US)",
volume = "53",
pages = "4745--4749",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

T1 - Evidence for oligoclonal T-cell response in a metastasis of renal cell carcinoma responding to vaccination with autologous tumor cells and transfer of in vitro-sensitized vaccine-draining lymph node lymphocytes

AU - Weidmann, Eckhart

AU - Logan, Theodore

AU - Yasumura, Satoshi

AU - Kirkwood, John M.

AU - Trucco, Massimo

AU - Whiteside, Theresa L.

PY - 1993/10/15

Y1 - 1993/10/15

N2 - Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) of a patient with von Hippel-Lindau disease and renal cell carcinoma were studied for the T-cell receptor β chain variable region (TCR-Vβ) repertoire. The patient was vaccinated with irradiated autologous tumor cells from a renal tumor mass, a vaccine-draining lymph node was removed, and lymphocytes were cultured in the presence of autologous tumor cells and low-dose interleukin 2 (IL2). These lymphocytes were adoptively transferred to the patient together with systemic IL2 (30,000 ID/kg every 8 h). Analysis of TCR-Vβ expression was performed by polymerase chain reaction in PBL before, during, and after therapy, in vaccine-draining lymph node lymphocytes, and in TIL obtained from moderately infiltrated, nonresponding renal tumor mass and from a more intensely infiltrated lung metastasis, which was responding to treatment. Significant differences in the expression of TCR-Vβ13.1 by T-cells recovered from these various sites were observed. Also, TIL recovered from the responding lung metastasis and cultured in the presence of IL2 gave rise to autologous tumor-reactive CD4+ T-cells, whereas the nonresponsive renal tumor yielded a mixture of T- and natural killer cells. In PBL obtained prior to treatment and during IL2 therapy, expression of Vβ13.1 was 0.7 and 1.8%, respectively, of the total Vβ gene repertoire. Fresh vaccine-draining lymph node lymphocytes contained 5.9% of Vβ13.1-expressing T-cells. After IL2 therapy, Vβ13.1 gene expression increased to 5.4% in PBL. In the nonresponding tumor mass, the frequency of Vβ13.1 gene expression among TIL was 12%, whereas in the responding, highly infiltrated nodule, it was 28%, with a striking loss of expression of other Vβ gene families. Sequencing of the amplified product of Vβ13.1 complementary DNA from the responding pulmonary metastasis showed restrictions in the complementarity-determining region 3. Thus, in vivo expansion of Vβ13.1-expressing CD4+ T-cells, possibly in response to a tumorassociated antigen, occurred in the responding tumor mass following this form of therapy and correlated with tumor course.

AB - Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) of a patient with von Hippel-Lindau disease and renal cell carcinoma were studied for the T-cell receptor β chain variable region (TCR-Vβ) repertoire. The patient was vaccinated with irradiated autologous tumor cells from a renal tumor mass, a vaccine-draining lymph node was removed, and lymphocytes were cultured in the presence of autologous tumor cells and low-dose interleukin 2 (IL2). These lymphocytes were adoptively transferred to the patient together with systemic IL2 (30,000 ID/kg every 8 h). Analysis of TCR-Vβ expression was performed by polymerase chain reaction in PBL before, during, and after therapy, in vaccine-draining lymph node lymphocytes, and in TIL obtained from moderately infiltrated, nonresponding renal tumor mass and from a more intensely infiltrated lung metastasis, which was responding to treatment. Significant differences in the expression of TCR-Vβ13.1 by T-cells recovered from these various sites were observed. Also, TIL recovered from the responding lung metastasis and cultured in the presence of IL2 gave rise to autologous tumor-reactive CD4+ T-cells, whereas the nonresponsive renal tumor yielded a mixture of T- and natural killer cells. In PBL obtained prior to treatment and during IL2 therapy, expression of Vβ13.1 was 0.7 and 1.8%, respectively, of the total Vβ gene repertoire. Fresh vaccine-draining lymph node lymphocytes contained 5.9% of Vβ13.1-expressing T-cells. After IL2 therapy, Vβ13.1 gene expression increased to 5.4% in PBL. In the nonresponding tumor mass, the frequency of Vβ13.1 gene expression among TIL was 12%, whereas in the responding, highly infiltrated nodule, it was 28%, with a striking loss of expression of other Vβ gene families. Sequencing of the amplified product of Vβ13.1 complementary DNA from the responding pulmonary metastasis showed restrictions in the complementarity-determining region 3. Thus, in vivo expansion of Vβ13.1-expressing CD4+ T-cells, possibly in response to a tumorassociated antigen, occurred in the responding tumor mass following this form of therapy and correlated with tumor course.

UR - http://www.scopus.com/inward/record.url?scp=0027496936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027496936&partnerID=8YFLogxK

M3 - Article

C2 - 8402652

AN - SCOPUS:0027496936

VL - 53

SP - 4745

EP - 4749

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 20

ER -