Recruitment of host CD8⁺ T cells by tumor-infiltrating lymphocytes and recombinant interleukin-2 during adoptive immunotherapy of cancer

Background. Previously we demonstrated that optimal doses of tumor-infiltrating lymphocytes (TIL) concomitant with recombinant interleukin-2 (rIL-2) effectively mediated complete tumor regression of murien 3-day pulmonary metastases. Methods. In the present study we have investigated the contribution of the host immune response to the effectiveness of adoptive immunotherapy with TIL in combination with low-dose rIL-2. All experiments were performed in a murine pulmonary metastases model induced by intravenous injection of methylcholanthrene-induced sarcoma (MCA-105) cells into C57BL/6 mice. As a novel approach we used monoclonal antibody specific for CD4⁺ or CD8⁺ T cells to deplete the host of its T-cell subpopulations. Results. Depletion of host CD8⁺ T cells 24 hours after tumor injection and 48 hours before TIL + rIL-2 treatment abrogated all antitumor activity of this type of immunotherapy and resulted in significant metastatic pulmonary disease (p<0.001). In contrast, depletion of host CD4⁺ T cells did not alter the efficacy of TIL + rIL-2 treatment in tumor eradication. The loss of tumoricidal activity of TIL + rIL-2 treatment in a CD8⁺ T cell-depleted host could be overcome by adding back normal uneducated splenocytes 2 hours after TIL therapy (p<0.001). In contrast, adding back CD8^- splenocytes to a CD8⁺ T cell-depleted host 2 hours after TIL + rIL-2 treatment resulted in significant pulmonary disease comparable to untreated animals. Conclusions. We conclude that the recruitment of host CD8⁺ T cells by adoptively transferred TIL + rIL-2 appears to be important for effective tumor eradication in this type of immunotherapy.