Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancerReportar como inadecuado

Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 2:11

First Online: 03 May 2002Received: 11 January 2002Accepted: 03 May 2002DOI: 10.1186-1471-2407-2-11

Cite this article as: Cao, Z.A., Daniel, D. & Hanahan, D. BMC Cancer 2002 2: 11. doi:10.1186-1471-2407-2-11


BackgroundIt is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction of their tumors. Thus, an important goal for tumor immunotherapy is to identify ways to modulate in vivo anti-tumor immunity to achieve clinical efficacy. We investigate this proposition in a spontaneous mouse tumor model, Rip1-Tag2.

MethodsExperimental therapies were carried out in two distinctive trial designs, intended to either intervene in the explosive growth of small tumors, or regress bulky end-stage tumors. Rip1-Tag2 mice received a single transfer of splenocytes from Tag-specific, CD4 T cell receptor transgenic mice, a single sub-lethal radiation, or a combination therapy in which the lymphocyte transfer was preceded by the sub-lethal radiation. Tumor burden, the extent of lymphocyte infiltration into solid tumors and host survival were used to assess the efficacy of these therapeutic approaches.

ResultsIn either intervention or regression, the transfer of Tag-specific T cells alone did not result in significant lymphocyte infiltration into solid tumors, not did it affect tumor growth or host survival. In contrast, the combination therapy resulted in significant reduction in tumor burden, increase in lymphocyte infiltration into solid tumors, and extension of survival.

ConclusionsThe results indicate that certain types of solid tumors may be intrinsically resistant to infiltration and destruction by tumor-specific T lymphocytes. Our data suggest that such resistance can be disrupted by sub-lethal radiation. The combinatorial approach presented here merits consideration in the design of clinical trials aimed to achieve T cell-mediated anti-tumor immunity.

AbbreviationsTCRT cell receptor

MHCmajor histocompatibility complex

H-2murine MHC locus

TagSV40 T antigen

RIPrat insulin promoter

RAGrecombinase activating gene.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-2-11 contains supplementary material, which is available to authorized users.

Zhu Alexander Cao, Dylan Daniel contributed equally to this work.

Autor: Zhu Alexander Cao - Dylan Daniel - Douglas Hanahan


Documentos relacionados