ADVERTISEMENT
Prognostic value of CD3+CD8+ T lymphocytes in advanced and metastatic PDAC
Background
T cells traffic into the tumor microenvironment, and exhibit cytotoxicity against tumor cells. Infiltration by cytotoxic CD3+CD8+ lymphocytes is associated with increased OS and DFS in PDAC (Orhan, 2020). There are some studies reflecting the prognostic value of circulating CD3+CD8+ cells in other cancer localisations. The proliferation potential of circulating CD8+ T cells was found to be a significant predictor for PFS in small cell lung cancer (An, 2019). The positive correlation between high CD3+CD8+ T cells and clinical results indicated the role in the prognosis of gastric cancer patients (He, 2017). We conduct one institution clinical trial to evaluate the prognostic and predictive value of different T lymphocyte subsets and other cells in the peripheral blood in patients with PDAC.
Methods
A cohort of 105 pts with advanced inoperable and metastatic PDAC was evaluated in this analysis. All patients undergoing systemic treatment in our institution and who signed informed consent were enrolled in the study. All patients were treated with mFOLFIRINOX or gemcitabine regimen for the 1st line. Blood samples were collected for analysis of T cell subsets, including CD19, CD3+ CD56+, CD8+ CD57+, CD3+ CD57+, CD3, CD3+ CD4+, CD3+ CD8+, CD3+ CD4- CD8, CD3- CD56+ CD16+, CD3- CD56+ CD16-, CD4+ CD25+ CD127+/-, CD4+ FOXP3+, CD8+ CD25+ CD127+/-, CD8+ FOXP3+ T cells by flow cytometry at initial diagnosis before chemotherapy. Results were estimated according to the age, sex, differentiation grade, presence of distant metastasis, number of metastatic sites, presence of ascites, body mass index, CA 19-9 values, chemotherapy regimen received, number of lines given after disease progression. Univariate Cox regression was used and survival curves were analyzed using the Kaplan–Meier method.
Results
There was a strong relationship between the presence of distant metastasis, the number of metastatic sites with PFS in our cohort. OS in addition to that was strongly associated with age, CA 19-9 level, number of following treatment lines. A quantity of circulating CD3+CD8+ cytotoxic T lymphocytes measured before treatment was found to be of prognostic value for both PFS (p=0.046) and OS (p= 0.031). Patients with higher than median 424,19 cells/MCL value demonstrated significantly better PFS and/or OS in the whole cohort as well as in the mFOLFIRINOX arm (p=0.037 for OS), in staging groups 4 (p=0,04 for PFS p=0.016 for OS) and 3 (p=0,049 for PFS) and G2 differentiation (p=0.03 for OS) arm. In gemcitabine arm and G3 tumors, low and high CD3+CD8+ survival differences didn‘t stand out. Lymphocyte count and CD3- CD56+CD16- T lymphocyte values before treatment also impact PFS but not OS. No other subset values at 1st visit and changes in means between 1st visit and 2nd visit 2 months later revealed an impact on PFS and OS.
Conclusions
The positive correlation between high CD3+CD8+ T cells and clinical outcome may show its‘ prognostic significance in advanced and metastatic pancreatic cancer patients and together with other well-known biomarkers, it could help in clinical decision making.
Legal entity responsible for the study
The author.
Funding
Vilnius University.
Disclosures
All authors have declared no conflicts of interest.
