Abstract
Background: Cancer-associated, major histocompatibility complex (MHC)-restricted peptide antigens
have been elucidated in human melanomas and ovarian, breast, and renal carcinomas;
but relatively little is known about lung cancer antigens. Methods: To work toward delineation of lung cancer–associated antigens, we developed tumor
infiltrating lymphocytes (TILs), peripheral blood mononuclear cell-derived cytolytic
T cell lines (CTL), autologous lung cancer cell lines, and normal lung cell lines
from 17 patients undergoing lung cancer resections. The TILs and CTL lines were subsequently
evaluated for markers of activation and specific lysis of autologous or allogeneic
lung cancer cell lines or both. Results: Freshly isolated TILs contained a more activated T cell population compared with
the patients' peripheral blood T cells as evidenced by an increased expression of
HLA-DR, CD25, and CD45RO. TILs isolated from 15 patients lysed allogeneic lung cancer
lines. TILs lysed autologous lung cancer but not autologous normal lung or Epstein-Barr
virus transformed B cell lines (B-LCL) in 4 of 8 cases tested, suggesting tumor specificity.
A CTL line (RHPBL57.1) was generated from peripheral blood mononuclear cells of an
HLA-A24+ patient by stimulation against an established HLA-A24+ allogeneic lung cancer cell line. RHPBL57.1 lysed the lung cancer cell line in an
HLA-A24–restricted manner. Moreover, RHPBL57.1 specifically lysed autologous B-LCL
pulsed with peptides, eluted from MHC class I and isolated from the HLA-A24+ lung cancer cell line. Conclusions: TILs isolated from patients with lung cancer are predominantly an activated population
of T cells with evidence of tumor and MHC class I–restricted lysis. Furthermore, we
provide evidence for a lung cancer–associated, MHC class I–bound peptide antigen(s)
that reconstitutes the epitope recognized by a lung cancer specific CD8+ T cell line derived from a patient with lung cancer. (Surgery 2000;128:76-85)
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References
- Direct analysis of tumor-associated peptide antigens.Curr Opin Immunol. 1994; 6: 733-740
- Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes.J Exp Med. 1995; 185: 363-368
- Human tumor antigens recognized by T lymphocytes.J Exp Med. 1996; 183: 725-729
- Identification of naturally processed human ovarian peptides recognized by tumor-associated CD8+ cytotoxic T lymphocytes.Cancer Res. 1997; 57: 87-93
- Tumor-specific and HLA-A2-restricted cytolysis by tumor associated lymphocytes in human metastatic breast cancer.J Immunol. 1995; 155: 4486-4491
- Bronchogenic carcinoma: immunologic aspects.Mayo Clin Proc. 1993; 68: 386-392
- HLA-A locus restricted and tumor-specific CTLs in tumor-infiltrating lymphocytes of patients with non-small cell lung cancer.Cell Immunol. 1997; 175: 101-110
- Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes.J Immunol. 1995; 155: 1343-1348
- Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines.Science. 1994; 264: 716-719
- Cytolytic T lymphocyte recognition of the immunodominant HLA-A0201-restricted Melan-A/MART-1 antigenic peptide in melanoma.J Immunol. 1997; 159: 2366-2374
- Specificity, T cell receptor diversity, and activation requirements of CD4+ and CD8+ clones derived from human melanoma-infiltrating lymphocytes.Eur J Immunol. 1992; 22: 1795-1802
- Dissociation of autologous and allogeneic mixed lymphocyte reactivity by using a monoclonal antibody specific for human T helper cells.J Immunol. 1983; 131: 2323-2327
- Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules.Nature. 1991; 351: 290-294
- Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor.Immunity. 1997; 6: 199-208
- Tumor escape from immune recognition.J Clin Invest. 1996; 98: 1633-1641
- A functionally defective allele of TAP 1 results in loss of MHC class I antigen presentation in a human lung cancer.Nat Genet. 1996; 2: 210-213
- Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance.Immunol Today. 1995; 16: 487-494
- Isolation of a kidney-specific peptide recognized by alloreactive HLA-A3 restricted human CTL.J Immunol. 1995; 154: 3880-3887
- Recognition of breast cancer-associated peptides by tumor-reactive, HLA-class I restricted allogeneic cytotoxic lymphocytes.Int J Cancer. 1999; 81: 607-615
- Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: functional and molecular characterization for their use in adoptive immunotherapy.Eur J Cancer. 1994; 30A: 97-102
- Phenotypes and lymphokine activated killer activity of pleural cavity lymphocytes of lung cancer patients without malignant effusion.Chest. 1993; 103: 1732-1738
- Cytotoxic T lymphocyte response to autologous human squamous cell cancer of the lung: epitope reconstitution with peptides extracted from HLA-Aw68.Cancer Res. 1994; 54: 2731-2737
- Functional characterization of T lymphocytes propagated from human lung carcinomas.Clin Immunol Immunopath. 1986; 38: 367-380
- Tumor-reactive T cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor.Cancer Res. 1992; 52: 775-781
- Human lung carcinomas express Fas ligand.Cancer Res. 1997; 6: 1007-1012
- Immunoglobulins cytophilic for human lymphocytes, monocytes, and neutrophils.J Clin Invest. 1975; 55: 368-376
- Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hot spots.Science. 1996; 274: 430-432
Article info
Publication history
Accepted:
February 21,
2000
Footnotes
*Supported by grants from the National Institutes of Health HL56643 and the American Heart Association.
**Reprint requests: T. Mohanakumar, PhD, Washington University School of Medicine, Department of Surgery, Box 8109-3326 CSRB, 660 S Euclid Ave, St Louis, MO 63110.
★*Current address: Department of Cell Biology, CINVESTAV-IPN, Mexico City.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
