Tumor masses support naive T cell infiltration, activation, and differentiation into effectors.
Studies of T cell responses to tumors have focused on the draining lymph node (LN) as the site of activation. We examined the tumor mass as a potential site of activation after adoptive transfer of naive tumor-specific CD8 T cells. Activated CD8 T cells were present in tumors within 24 h of adoptive transfer and proliferation of these cells was also evident 4-5 d later in mice treated with FTY720 to prevent infiltration of cells activated in LNs. To confirm that activation of these T cells occurred in the tumor and not the tumor-draining LNs, we used mice lacking LNs. Activated and proliferating tumor-infiltrating lymphocytes were evident in these mice 24 h and 4 d after naive cell transfer. T cells activated within tumors acquired effector function that was evident both ex vivo and in vivo. Both cross-presenting antigen presenting cells within the tumor and tumor cells directly presenting antigen activated these functional CD8 effectors. We conclude that tumors support the infiltration, activation, and effector differentiation of naive CD8 T cells, despite the presence of immunosuppressive mechanisms. Thus, targeting of T cell activation to tumors may present a tool in the development of cancer immunotherapy.
Thompson
Elizabeth D
ED
Department of Microbiology and Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
Enriquez
Hilda L
HL
Fu
Yang-Xin
YX
Engelhard
Victor H
VH
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D040881:CD11a Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics; D000068876:Fingolimod Hydrochloride; D053804:Granzymes / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D039441:Integrin alpha4 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011409:Propylene Glycols / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000235:genetics; D052118:Lysosomal-Associated Membrane Protein 1
D040881:CD11a Antigen; D004268:DNA-Binding Proteins; D000068876:Fingolimod Hydrochloride; D053804:Granzymes; D018960:Hyaluronan Receptors; D007166:Immunosuppressive Agents; D039441:Integrin alpha4; D007371:Interferon-gamma; D051907:Lysosomal Membrane Proteins; D014442:Monophenol Monooxygenase; D010047:Ovalbumin; D010446:Peptide Fragments; D011409:Propylene Glycols; D011948:Receptors, Antigen, T-Cell; D013110:Sphingosine; D001613:beta 2-Microglobulin; C476399:Cd44 protein, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C110366:OVA-8; C499308:Rag2 protein, mouse; C509214:Gzmb protein, mouse