Abstract
In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNγ-producing memory CD8+ T cells act as "helper" cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type "heterologous" (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and helper functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of helper functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 10012-10018 |
| Number of pages | 7 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 20 |
| DOIs | |
| State | Published - Oct 15 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Helper function of memory CD8+ T cells : Heterologous CD8 + T cells support the induction of therapeutic cancer immunity. / Nakamura, Yutaro; Watchmaker, Payal; Urban, Julie; Sheridan, Brian; Giermasz, Adam; Nishimura, Fumihiko; Sasaki, Kotaro; Cumberland, Rachel; Muthuswamy, Ravikumar; Mailliard, Robbie B.; Larregina, Adriana T.; Falo, Louis D.; Gooding, William; Storkus, Walter J.; Okada, Hideho; Hendricks, Robert L.; Kalinski, Pawel.
In: Cancer Research, Vol. 67, No. 20, 15.10.2007, p. 10012-10018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Helper function of memory CD8+ T cells
T2 - Heterologous CD8 + T cells support the induction of therapeutic cancer immunity
AU - Nakamura, Yutaro
AU - Watchmaker, Payal
AU - Urban, Julie
AU - Sheridan, Brian
AU - Giermasz, Adam
AU - Nishimura, Fumihiko
AU - Sasaki, Kotaro
AU - Cumberland, Rachel
AU - Muthuswamy, Ravikumar
AU - Mailliard, Robbie B.
AU - Larregina, Adriana T.
AU - Falo, Louis D.
AU - Gooding, William
AU - Storkus, Walter J.
AU - Okada, Hideho
AU - Hendricks, Robert L.
AU - Kalinski, Pawel
PY - 2007/10/15
Y1 - 2007/10/15
N2 - In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNγ-producing memory CD8+ T cells act as "helper" cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type "heterologous" (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and helper functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of helper functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections.
AB - In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNγ-producing memory CD8+ T cells act as "helper" cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type "heterologous" (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and helper functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of helper functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections.
UR - http://www.scopus.com/inward/record.url?scp=35448963393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35448963393&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-1735
DO - 10.1158/0008-5472.CAN-07-1735
M3 - Article
C2 - 17942935
AN - SCOPUS:35448963393
VL - 67
SP - 10012
EP - 10018
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 20
ER -