Abstract
ObjectiveEnhancing immunologic responses, including human leukocyte antigen (HLA) class I expression on tumor cells and recognition and elimination of tumor cells by tumor-specific cytotoxic T lymphocyte (CTL), is considered a novel concept of radiotherapy. The present study examined patients who underwent preoperative hyperthermo-chemoradiotherapy (HCRT) for locally advanced rectal cancer to assess the correlation between HLA class I expression and clinical outcome.Materials and MethodsSeventy-eight patients with locally advanced rectal adenocarcinoma who received preoperative HCRT were enrolled. The median age of the patients was 64 years (range, 33–85 years) and 4, 18, and 56 patients had clinical stage I, II and III disease, respectively. Formalin-fixed and paraffin-embedded tissues excised before and after HCRT were subjected to immunohistochemical analysis with an anti-HLA class I-A, B, C antibody. HLA class I expression was graded according to tumor cell positivity.ResultsIn pre-HCRT, the number of specimens categorized as Grade 0 and 1 were 19 (24%) and 58 (74%), respectively. Only 1 patient (1%) showed Grade 2 expression. However, 6 (8%), 27 (35%), 7 (9%), and 12 (15%) post-HCRT specimens were graded as Grade 0, 1, 2, and 3, respectively. There was a significant increase in HLA class I expression in post-HCRT specimens (p<0.01). However, neither pre- nor post-HCRT HLA class I expression affected overall survival and distant metastasis-free survival in clinical stage III patients. Univariate analysis revealed that Post-HCRT HLA class I expression showed a significant negative relationship with LC (p<0.05). Nevertheless, multivariate analysis showed that there was no correlation between HLA class I expression and clinical outcome.ConclusionHCRT increased HLA class I expression in rectal cancer patients. However, multivariate analysis failed to show any correlation between the level of HLA class I expression and prognosis.
Highlights
Accumulating evidence supports the importance of cell-mediated immunity for controlling tumor growth and eliminating distant metastases [1]
There was a significant increase in Human leukocyte antigen (HLA) class I expression in post-HCRT specimens (p,0.01)
Univariate analysis revealed that Post-HCRT HLA class I expression showed a significant negative relationship with local control rate (LC) (p,0.05)
Summary
Accumulating evidence supports the importance of cell-mediated immunity for controlling tumor growth and eliminating distant metastases [1]. Many studies report a significant correlation between clinical prognosis and the expression of HLA class I by esophageal, non-small cell lung, head and neck squamous cell, and bladder cancers [3,4,5,6,7,8]. The concept underlying radiation-induced immunogenic cell death is based on the induction of anti-tumor immune CTL responses by radiotherapy with modification of the immunogenic epitopes on tumor HLA class I molecules. Few reports have examined the correlation between radiotherapy and HLA expression on tumor cells in a clinical setting [12,14,15]. To the best of our knowledge, no studies have examined changes in HLA class I expression by tumor cells in the same patient before and after radiotherapy
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