Anti-VEGF and Anti-EGFR Antibody Therapy on T-Cell Infiltration and TCR Variation in Metastatic Colorectal Cancer

Ming Xu
Ryouichi Tsunedomi
Kazuma Kiyotani
Shinobu Tomochika
Kei Furuya
Masao Nakajima
Hiroto Matsui
Yukio Tokumitsu
Yoshitaro Shindo
Shin Yoshida
Michihisa Iida
Nobuaki Suzuki
Shigeru Takeda
Tatsuya Ioka
Shoichi Hazama
Hiroaki Nagano

BACKGROUND/AIM: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases. MATERIALS AND METHODS: Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3+ T-cell infiltration. RESULTS: T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group. CONCLUSION: The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.

Anticancer research

43

2

613

620

10.21873/anticanres.16197

https://doi.org/10.21873/anticanres.16197
https://www.ncbi.nlm.nih.gov/pubmed/36697107