The association of clinical outcome and peripheral T-cell subsets in metastatic colorectal cancer patients receiving first-line FOLFIRI plus bevacizumab therapy

ABSTRACT

The first-line standard of care for patients with metastatic colorectal cancer (mCRC) is FOLFIRI (irinotecan, levo-leucovorin, 5-fluorouracil (5-FU)) plus bevacizumab. With the renewed interest in cancer immunotherapy with agents such as vaccines, checkpoint inhibitors and immune modulators, the possibility exists for the use of one or more of these immunotherapeutics in the first-line setting and thus in combination with the FOLFIRI and bevacizumab regimen. Studies were undertaken to study the effects of FOLFIRI and bevacizumab therapy on peripheral T-cell subsets, and to determine if there are any associations between these subsets and response to therapy. Peripheral blood mononuclear cell subsets of patients with mCRC (n = 23) were analyzed prior to and during therapy. While there were differences among patients, the majority of patients showed either a minimal change or an increase in CD4⁺ T cell to regulatory T cell (Treg) ratios during therapy, as well as either minimal change or a decrease in Treg suppressive activity during therapy. There was also an association (p = 0.036) between a decrease in Treg frequency during FOLFIRI therapy and overall survival, and an association (p = 0.037) between the frequency of Tregs prior to therapy and progression-free survival. Responders to the chemotherapy by RECIST criteria also had a greater decrease in Tregs during therapy vs. pre-therapy (p = 0.0064) as compared to non-responders. While the number of mCRC patients undergoing chemotherapy in this study is relatively small, it provides the rationale for the use of immunotherapeutics in this first-line metastatic setting.

KEYWORDS:

• Chemotherapy
• colorectal cancer
• FOLFIRI
• immunotherapy
• peripheral T cells
• Tregs

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors thank Debra Weingarten for her editorial assistance in the preparation of the manuscript.

Funding

This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. This work has been partially carried out within the Ph.D. program in “Medicina Sperimentale e dei Sistemi” XXXI Ciclo, Tor Vergata University, Rome, Italy.