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Peptidome from Renal Cell Carcinoma Contains Antigens Recognized by CD4⁺ T Cells and Shared among Tumors of Different Histology

Authors' Affiliations: ¹ Tumor Immunology Unit, DIBIT, ² Experimental Immunology Unit, ³ Cancer Immunotherapy and Gene Therapy Program, ⁴ Pathology Unit, ⁵ Medicine Unit, and ⁶ Department of Oncology, Scientific Institute H. San Raffaele, Milan, Italy

Requests for reprints: Maria Pia Protti, Tumor Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DIBIT, Scientific Institute H. San Raffaele, Via Olgettina 58, 20132 Milan, Italy. Phone: 39-02-2643-4185; Fax: 39-02-2643-4786; E-mail: m.protti{at}hsr.it.

Purpose: Renal cell carcinoma (RCC) is considered immunogenic; nonetheless, rare tumor-associated antigens have been identified or are expressed in RCC. Peptidome (i.e., the total content of natural peptides of whole cells) from other tumors, such as melanoma, has proved to be immunogenic. The aims of this study were to determine whether peptidome from RCC is immunogenic and whether it contains tumor peptides shared among allogenic RCCs.

Experimental Design: Autologous dendritic cells pulsed with RCC peptidome were used to activate in vitro CD4⁺ T cells from healthy donors and a metastatic RCC patient. CD4⁺ T-cell polyclonal lines and clones were characterized for tumor cell recognition by proliferation assay, killing activity, and cytokine secretion.

Results: CD4⁺ T-cell lines and clones recognized HLA-DR-matched allogenic RCC and, for the patient, the autologous tumor. RCC-reactive CD4⁺ T cells showed a heterogeneous Th1 or Th0/Th2 pattern of cytokine secretion. Moreover, RCC-reactive CD4⁺ T cells recognized also melanoma, colon carcinoma, cervical carcinoma, pancreas carcinoma, lung carcinoma, gastric carcinoma, and lymphoma cells but not autologous T-cell blasts.

Conclusions: Our results show that (a) the RCC peptidome contain antigens recognized by CD4⁺ T cells and (b) shared among tumors of different histology and (c) it induces both Th1-type and Th2/Th0-type immune responses. These data support the use of the peptidome from allogenic RCC for specific immunotherapy in RCC and possibly in other neoplastic diseases. Moreover, the CD4⁺ T-cell clones generated here are useful tools for tumor antigen identification.

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