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Impairment of lymphocyte locomotion in the tumor microenvironment and the effect of systemic immunotherapy with liposome-encapsulated myramyl-tripeptide-phosphatidylethanolamine

  • Original Article
  • Locomotion, TIL, Imminotherapy MTP-PE
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Abstract

The ability of the lymphocytes to move through the interstitium is obligatory to the immune response. We previously showed that tumor-infiltrating lymphocytes (TIL) from human melanoma and renal cell carcinoma demonstrate a dramatic decrease in their spontaneous locomotion through three-dimensional collagen gel when compared with peripheral blood lymphocytes (PBL) and lymph node lymphocytes. To determine if this decrease is caused by contact with tumor cells, or mediated through certain diffusible factors, we examined the effects of autologous tumor cells on the locomotion of PBL in a model system where tumor cells were separated from lymphocytes by a 3-mm layer of gelled collagen. After 21–22 h incubation in chamber slides, locomotion distances were assessed in the presence and absence of tumor and normal cells. In the presence of tumor cells. PBL from 14 of 18 patients displayed substantial (466.5±2.7 μm compared to control 568.9±10.9 μm,P<0.001), loss of motility. Inhibition was more prominent in melanoma patients than in renal cell carcinoma patients. Thus the impaired locomotion previously observed in TIL was at least partially due to the presence of tumor. The locomotion of TIL was restored in four of five melanoma patients treated with liposome-encapsulated muramyltripeptide-phosphatidylethanolamine (L-MTP-PE). Furthermoe, in six of seven examined L-MTP-PE-treated patients, an increase in intrinsic PBL locomotion during the first month of the therapy was observed. These results suggest that the environment of the tumor is not conducive to locomotion of advancing lymphocytes and the therapeutic intervention may ameliorate the loss of lymphocytic infiltration.

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Author information

Author notes

  1. Diana Risin & Roland P. Pizzini

    Present address: Biotechnology, BT/37, KRUG Life Sciences, 1290 Hercules Drive, 77058, Houston, TX, USA

  2. Neal R. Pellis

    Present address: Biotechnology Program-AD4, NASA/Johnson Space Center, NASA Road 1, 77058, Houston, TX, USA

  3. Yasuiki Umezu

    Present address: The Department of Oral and Maxillofacial Surgery, Tohoku University School of Medicine, 980, Sendai, Japan

Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Box 174, 77030, Houston, IX, USA

    Diana Risin, Roland P. Pizzini, Charles M. Balch & Neal R. Pellis

  2. Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, 77030, Houston, TX, USA

    Eugenie S. Kleinerman, Yasuiki Umezu & Neal R. Pellis

  3. Department of Immunology, The University of Texas M. D. Anderson Cancer Center, 77030, Houston, TX, USA

    Yasuiki Umezu & Neal R. Pellis

Authors
  1. Diana Risin
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Additional information

This work was supported by the Gillson-Longenbaugh Foundation. Texas Higher Education Advanced Technology Program (ATP) grant 000015-131, NASA grant NAG-9-664, a grant from the Tenneco Corp. from the Division of Surgery Core Facility, and NIH grant CA 42992

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Risin, D., Kleinerman, E.S., Umezu, Y. et al. Impairment of lymphocyte locomotion in the tumor microenvironment and the effect of systemic immunotherapy with liposome-encapsulated myramyl-tripeptide-phosphatidylethanolamine. Cancer Immunol Immunother 40, 57–64 (1995). https://doi.org/10.1007/BF01517236

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  • DOI: https://doi.org/10.1007/BF01517236

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