Dynamic monitoring the TCR CDR3 spectratypes in patients with metastatic CRC treated with a combination of bevacizumab, irinotecan, fluorouracil, and leucovorin.
In the present study, either modified IFL regimen (modified irinotecan, fluorouracil and leucovorin, mIFL) alone or in combination with bevacizumab was used to treat patients with metastatic colorectal cancer (CRC). Treatment efficacy was assessed using coupled tomography imaging diagnosis. The toxicity accompany with treatment was evaluated, as well as T cell receptor (TCR) repertoire before and several cycles after therapy was dynamically monitored by analyzing the complementarity-determining region 3 (CDR3) length distribution within CD4(+) and CD8(+) T cell subsets. The degrees of normalization of the T cell repertoire in CRC patients treated with the two methods were compared. The results showed that mIFL combined with bevacizumab was more effective in treating patients with metastatic CRC, and was accompanied by an increase in side effects such as proteinuria and hematuria. An even more restricted CDR3 profile in patients with metastatic CRC compared with healthy control has been detected. A prominent usage of TCR beta chain variable (BV) gene BV12 and BV16 families within the CD4(+) T cell subset and BV19 and BV21 families within the CD8(+) T cell subset have been found before treatment. Moreover, CD8(+) T cells showed more restricted patterns than CD4(+) T cells, especially in patients before treatment. For patients with stable disease (SD) or partial remission (PR) after treatment, a less restricted CDR3 profile in post-treatment compared with pre-treatment has been found, but the opposite result was observed for patients with progressive disease (PD). The less restricted CDR3 pattern suggested a trend toward normalization of the TCR repertoire. The normalization of TCR repertoire significantly increased in patients treated with mIFL in combination with bevacizumab, but slightly in patients treated with mIFL alone. The results demonstrate a positive correlation between post-therapy TCR repertoire normalization and remission of metastatic CRC.
Luo
Wei
W
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China.
Liao
Wang-Jun
WJ
Ma
Li
L
Huang
Yong-Ta
YT
Shi
Min
M
Wen
Qian
Q
Wang
Xiao-Ning
XN
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D022801:Complementarity Determining Regions / Q000032:analysis*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D019674:Genes, T-Cell Receptor beta; D006417:Hematuria / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin