The association of clinical outcome and peripheral T-cell subsets in metastatic colorectal cancer patients receiving first-line FOLFIRI plus bevacizumab therapy.
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.
Medical Oncology, Department of Systems Medicine, Tor Vergata University Clinical Center, University of Rome Tor Vergata , Rome, Italy.
Mario
M
Roselli
Medical Oncology, Department of Systems Medicine, Tor Vergata University Clinical Center, University of Rome Tor Vergata , Rome, Italy.
Vincenzo
V
Formica
Medical Oncology, Department of Systems Medicine, Tor Vergata University Clinical Center, University of Rome Tor Vergata , Rome, Italy.
Vittore
V
Cereda
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Caroline
C
Jochems
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Jacob
J
Richards
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Italia
I
Grenga
Anatomic Pathology Institute, Department of Biomedicine and Prevention, University of Rome Tor Vergata , Rome, Italy.
Augusto
A
Orlandi
Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University , Rome, Italy.
Patrizia
P
Ferroni
Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy; Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy.
Fiorella
F
Guadagni
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Jeffrey
J
Schlom
Chemotherapy; FOLFIRI; Tregs; colorectal cancer; immunotherapy; peripheral T cells