Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment.
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.
Department of Pathology, University of Chicago, 5841 S Maryland Ave., Chicago, IL 60637, USA.
Youjin
Y
Lee
Sogyong L
SL
Auh
Yugang
Y
Wang
Byron
B
Burnette
Yang
Y
Wang
Yuru
Y
Meng
Michael
M
Beckett
Rohit
R
Sharma
Robert
R
Chin
Tony
T
Tu
Ralph R
RR
Weichselbaum
Yang-Xin
YX
Fu
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000532:radiotherapy*; D011878:Radiotherapy; D047368:Tumor Burden / Q000276:immunology