JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Polyfunctional CD4⁺ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy.

Blood 2012 September 14
The finding that many chemotherapeutic agents have immunostimulatory effects has provided the impetus to combine chemotherapy and immunotherapy for synergistic antitumor effects. However, the critical determinants of effective antitumor immunity after chemotherapy have not been defined. Here we report that adoptive transfer of tumor-specific CD4⁺ T cells after chemotherapy with cyclophosphamide gave rise to polyfunctional CD4⁺ effector cells, which in turn intensified the inflammatory milieu and enhanced the activation of CD8⁺ T cells in the tumor microenvironment. Although this combined chemoimmunotherapy initially resulted in progressive regression of advanced B-cell lymphoma, its therapeutic efficacy was not durable and most mice succumbed to late relapse. Notably, relapse was associated with acquisition of a tolerized phenotype in tumor-specific CD4⁺ T cells, characterized by overexpression of program death-1 (PD-1). Remarkably, effective antitumor immunity was maintained and cure became prevalent when polyfunctional CD4⁺ effector cells were prevented from undergoing PD-1-mediated tolerization, either by antibody blockade of the PD-1-PD-L1 pathway, or targeted ablation of PD-1 in tumor-specific CD4⁺ T cells. Our study suggests that tumor-reactive CD4⁺ T cells act as the "gatekeepers" of the host antitumor immunity in the postchemotherapy setting, thereby their functional status governs the choice between eradication versus regrowth of residual tumors.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app