Mammary tumors with diverse immunological phenotypes show differing sensitivity to adoptively transferred CD8+ T cells lacking the Cbl-b gene.
We tested the efficacy of CD8+ T cells lacking the Cbl-b gene against a panel of mammary tumor lines with different intrinsic sensitivities to T cells. Mice bearing established tumors expressing an ovalbumin-tagged version of HER-2/neu underwent adoptive transfer with Cbl-b-replete or -null CD8+ T cells from OT-I T cell receptor transgenic donor mice. In general, Cbl-b-null OT-I cells showed enhanced expansion, persistence, and capacity for tumor infiltration. This resulted in markedly enhanced efficacy against two tumor lines that normally demonstrate complete (NOP21) or partial (NOP23) regression. Moreover, a third tumor line (NOP6) that normally demonstrates progressive disease underwent complete regression in response to Cbl-b-null OT-I cells. However, a fourth tumor line (NOP18) was resistant to Cbl-b-null OT-I cells owing to a profound barrier to lymphocyte infiltration. Thus, Cbl-b-null CD8+ T cells are generally more efficacious but are nonetheless unable to mediate curative responses against all tumor phenotypes.
Yang
Taimei
T
Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, 2410 Lee Avenue, Victoria, BC V8R 6V5, Canada.
Martin
Michele L
ML
Nielsen
Julie S
JS
Milne
Katy
K
Wall
Erika M
EM
Lin
Wendy
W
Watson
Peter H
PH
Nelson
Brad H
BH
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D051858:Forkhead Transcription Factors / Q000502:physiology; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050721:Proto-Oncogene Proteins c-cbl