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 Blood, 16 July 2009, Vol. 114, No. 3, pp. 589-595.
Prepublished online as a Blood First Edition Paper on April 6, 2009; DOI 10.1182/blood-2009-02-206870.

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IMMUNOBIOLOGY

Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment

Youjin Lee1,*, Sogyong L. Auh1,*, Yugang Wang1, Byron Burnette1, Yang Wang1, Yuru Meng2, Michael Beckett2, Rohit Sharma3, Robert Chin1, Tony Tu1, Ralph R. Weichselbaum2, and Yang-Xin Fu1

1 Department of Pathology, 2 Department of Radiation and Cellular Oncology/Ludwig Center for Metastasis Research, and 3 Department of Surgery, University of Chicago, IL

Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.


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Related Article in Blood Online:

Ablative RT protects immune responses
Anatoly Dritschilo
Blood 2009 114: 497-498. [Full Text] [PDF]



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A. Dritschilo
Ablative RT protects immune responses
Blood, July 16, 2009; 114(3): 497 - 498.
[Full Text] [PDF]


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