This paper is only available as a PDF. To read, Please Download here.
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.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes.Science. 1986; 233: 1318-1321
- In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2.J Natl Cancer Inst. 1987; 79: 1067-1075
- The biological effects of immunosuppression on cellular immunotherapy.Surg Oncol. 1992; 1: 27-35
- T-cell mediated suppression of antitumor immunity.J Exp Med. 1980; 151: 69-80
- T-cell mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases.J Exp Med. 1981; 154: 1033-1042
- Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells.J Exp Med. 1982; 155: 1063-1074
- Generation and decay of the immune response to a progressive fibrosarcoma.J Exp Med. 1984; 159: 1312-1321
- Adoptive immunotherapy of newly induced murine sarcomas.Cancer Res. 1985; 45: 1657-1662
- Synergistic antitumor activity of tumor-infiltrating lymphocytes, interleukin 2, and local tumor irradiation.J Exp Med. 1990; 171: 249-263
- Generation of lymphokine-activated killer cells does not require DNA synthesis.Immunology. 1987; 60: 471-473
- Solid-phase anti-CD3 antibody activation of murine tumor-infiltrating lymphocytes.Cancer Res. 1990; 50: 2587-2592
- Serologic identification of multiple tumor-associated antigens on murine sarcomas.J Natl Cancer Inst. 1977; 58: 1303-1309
- The anti-tumor efficacy of lympholine-activated killer cells and recombinant interleukin-2 in vivo.J Immunol. 1985; 135: 646-652
- A comparative morphological study of the mammary gland in a high and low tumor strain of mice.Am J Pathol. 1938; 14: 557-578
- Accurate identification of experimental pulmonary metastases.J Natl Cancer Inst. 1966; 36: 641-645
- A generalized Wilcoxon test for comparing arbitrarily singly-censored samples.Biometrica. 1965; 52: 203-217
- Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials.J Immunol Methods. 1987; 102: 127-141
- Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study.J Clin Oncol. 1988; 6: 839-853
- Use of tumorinfiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma.N Engl J Med. 1988; 319: 1676-1680
- Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response.J Natl Cancer Inst. 1991; 83: 932-937
- A new regimen of interleukin 2 and lymphokine-activated killer cells.Arch Intern Med. 1988; 148: 2571-2576
- Immunomodulatory effects of systemic lowdose recombinant interleukin-2 and lymphokine-activated killer cells in humans.Cancer Immunol Immunother. 1989; 30: 145-150
- Interferon γ and tumor necrosis factor have a role in tumor regression mediated by murine CD8+ tumor-infiltrating lymphocytes.J Exp Med. 1991; 173: 647-658
- Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon γ.J Exp Med. 1993; 178: 151-161
- Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2.J Immunol. 1987; 139: 285-294
- Activation of CD8+ murine T cells from tumor-draining lymph nodes by phorbol dibutyrate plus calcium ionophore.J Immunother. 1992; 12: 32-40
- Cellular mechanisms of the antitumor activity of recombinant IL-6 in mice.J Immunol. 1992; 148: 2622-2629
- Defective presentation of endogenous antigens by a murine sarcoma.J Immunol. 1991; 147: 1453-1459
- Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin-2.J Exp Med. 1982; 156: 385-397
- Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin-2.Cancer Res. 1985; 45: 3735-3741
- Generation of T cells reactive to poorly immunogenic B16-BL6 melanoma with efficacy in the treatment of spontaneous metastases.J Immunother. 1993; 13: 153-165
- (Re) Activation of murine tumor-infiltrating lymphocytes with solidphase anti-CD3 antibody: in vitro cytokine production is associated with in vivo efficacy.Surg Oncol. 1994; 3: 79-89
- The biology of interleukin-6.Blood. 1989; 74: 1-10
- Direct activation of human resting T cells by IL-2: the role of an IL-2 receptor distinct from the Tac protein.J Immunol. 1987; 139: 1550-1556
Article info
Publication history
Accepted:
June 27,
1994
Footnotes
*Supported by the National Institutes of Health grant CA 45484 and the American Cancer Society Faculty Research Award FRA-407.
Identification
Copyright
© 1995 Mosby-Year Book, Inc. Published by Elsevier Inc.
