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 F. Logan, Satoshi Yasumura, John M. Kirkwood, Massimo Trucco, Theresa L. Whiteside

Research output: Contribution to journalArticle

37 Scopus citations

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 IU/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 tumor-associated 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 1993

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this