Abstract
The systemic adoptive transfer of tumor-sensitized T cells, activated ex vivo, can eliminate established intracranial tumors. Regression of MHC class II negative MCA 205 fibrosarcomas occurs optimally following adoptive transfer of both CD4 and CD8 tumor-sensitized T cells, indicating an important function for tumor-infiltrating APC. Here, we demonstrate that during an effector response, indirect presentation of tumor Ags to transferred T cells is sufficient to mediate intracranial tumor regression. BALB/c → CB6F1 (H-2bxd) bone marrow chimeras were challenged with the MCA 205 fibrosarcoma (H-2b). The tumor grew progressively in the H-2b-tolerant chimeras and stimulated an immune response in tumor-draining lymph nodes. Tumor-sensitized lymph node T cells were activated ex vivo with anti-CD3 and IL-2, then adoptively transferred to sublethally irradiated BALB/c or C57BL/6 recipients bearing established intracranial MCA 205 tumors. The transferred T cells eradicated MCA 205 tumors in BALB/c recipients and demonstrated tumor specificity, but had no therapeutic efficacy in the C57BL/6 recipients. These data establish that tumor-associated host cell constituents provide sufficient Ag presentation to drive effector T cell function in the complete absence of direct tumor recognition. This effector mechanism has an evident capacity to remain operative in circumstances of immune escape, where the tumor does not express the relevant MHC molecules, and may have importance even at times when direct CTL recognition also remains operative.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3656-3662 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 165 |
| Issue number | 7 |
| State | Published - Oct 1 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Cross-presentation of tumor antigens to effector T cells is sufficient to mediate effective immunotherapy of established intracranial tumors. / Plautz, G. E.; Mukai, S.; Cohen, Peter A; Shu, S.
In: Journal of Immunology, Vol. 165, No. 7, 01.10.2000, p. 3656-3662.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cross-presentation of tumor antigens to effector T cells is sufficient to mediate effective immunotherapy of established intracranial tumors
AU - Plautz, G. E.
AU - Mukai, S.
AU - Cohen, Peter A
AU - Shu, S.
PY - 2000/10/1
Y1 - 2000/10/1
N2 - The systemic adoptive transfer of tumor-sensitized T cells, activated ex vivo, can eliminate established intracranial tumors. Regression of MHC class II negative MCA 205 fibrosarcomas occurs optimally following adoptive transfer of both CD4 and CD8 tumor-sensitized T cells, indicating an important function for tumor-infiltrating APC. Here, we demonstrate that during an effector response, indirect presentation of tumor Ags to transferred T cells is sufficient to mediate intracranial tumor regression. BALB/c → CB6F1 (H-2bxd) bone marrow chimeras were challenged with the MCA 205 fibrosarcoma (H-2b). The tumor grew progressively in the H-2b-tolerant chimeras and stimulated an immune response in tumor-draining lymph nodes. Tumor-sensitized lymph node T cells were activated ex vivo with anti-CD3 and IL-2, then adoptively transferred to sublethally irradiated BALB/c or C57BL/6 recipients bearing established intracranial MCA 205 tumors. The transferred T cells eradicated MCA 205 tumors in BALB/c recipients and demonstrated tumor specificity, but had no therapeutic efficacy in the C57BL/6 recipients. These data establish that tumor-associated host cell constituents provide sufficient Ag presentation to drive effector T cell function in the complete absence of direct tumor recognition. This effector mechanism has an evident capacity to remain operative in circumstances of immune escape, where the tumor does not express the relevant MHC molecules, and may have importance even at times when direct CTL recognition also remains operative.
AB - The systemic adoptive transfer of tumor-sensitized T cells, activated ex vivo, can eliminate established intracranial tumors. Regression of MHC class II negative MCA 205 fibrosarcomas occurs optimally following adoptive transfer of both CD4 and CD8 tumor-sensitized T cells, indicating an important function for tumor-infiltrating APC. Here, we demonstrate that during an effector response, indirect presentation of tumor Ags to transferred T cells is sufficient to mediate intracranial tumor regression. BALB/c → CB6F1 (H-2bxd) bone marrow chimeras were challenged with the MCA 205 fibrosarcoma (H-2b). The tumor grew progressively in the H-2b-tolerant chimeras and stimulated an immune response in tumor-draining lymph nodes. Tumor-sensitized lymph node T cells were activated ex vivo with anti-CD3 and IL-2, then adoptively transferred to sublethally irradiated BALB/c or C57BL/6 recipients bearing established intracranial MCA 205 tumors. The transferred T cells eradicated MCA 205 tumors in BALB/c recipients and demonstrated tumor specificity, but had no therapeutic efficacy in the C57BL/6 recipients. These data establish that tumor-associated host cell constituents provide sufficient Ag presentation to drive effector T cell function in the complete absence of direct tumor recognition. This effector mechanism has an evident capacity to remain operative in circumstances of immune escape, where the tumor does not express the relevant MHC molecules, and may have importance even at times when direct CTL recognition also remains operative.
UR - http://www.scopus.com/inward/record.url?scp=0034292408&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034292408&partnerID=8YFLogxK
M3 - Article
C2 - 11034369
AN - SCOPUS:0034292408
VL - 165
SP - 3656
EP - 3662
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -