Comparison of dynamic changes in the peripheral CD8+ T cells function and differentiation in ESCC patients treated with radiotherapy combined with anti-PD-1 antibody or concurrent chemoradiotherapy

Abstract

ObjectiveThe systematic immune status of cancer patients undergoing immunotherapy is little known. We prospectively identified the function and differentiation traits of peripheral CD8+ T cells based on our phase 1b clinical trial (NCT03222440) of radiotherapy combined with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and compared it with concurrent chemoradiotherapy (CCRT).Methods19 and 18 patients were included in the cohort of radiotherapy plus camrelizumab and cohort of CCRT treatment. By using flow cytometry, we evaluated the expression levels of PD-1, Eomes, T-bet and IFN-γ (function), CD38 and HLA-DR (activation), and differentiation subsets classified according to the expression levels of CD45RA and CD62L in peripheral CD8+ T cells before and during treatment.ResultsEffective binding of anti-PD-1 antibody camrelizumab with PD-1 on CD8+ T cells was detected during treatment. Both two treatments elevated the expression levels of activation molecules CD38 and HLA-DR on CD8+ T cells. PD-1+CD8+ T cells had more activation features than PD-1-CD8+ T cells in two groups and the treatments did not alter these differences. The two treatments activated both PD-1+ and PD-1- CD8+ T cells. PD-1+CD8+ T cells had less Naïve and TEMRA but more Tcm and Tem than PD-1-CD8+ T cells in two groups and both two treatments changed the ratio of memory T cells in PD-1+ and PD-1- cells. RT plus camrelizumab treatment reduced Naïve T cells and TEMRA subsets both in PD-1+ and PD-1- CD8+ T cells while elevated Tcm subset in PD-1+CD8+ T cells and Tem subset in PD-1-CD8+ T cells. CCRT elevated Tcm subset and reduced TEMRA subset in PD-1-CD8+ T cells while did not change any subset in PD-1+CD8+ T cells. Furthermore, patients undergoing radiotherapy plus immunotherapy were found to obtain better prognosis than those receiving CCRT.ConclusionsThis study identified the dynamic changes of systematic immune status of patients undergoing treatment. The two treatments had similar activation effects on peripheral CD8+ T cells with different PD-1 properties but had different effects on their differentiation status. These results provided potential clues to the reasons underlying the difference in prognosis of the two treatments.

Peripheral Blood CD8+ T-Lymphocyte Subsets Are Associated with Prognosis in Prostate Cancer Patients

“…We also found higher percentages of CD8+ TEMRA cells in the patient cohort with metastatic disease, suggesting that these may have a restricted capacity for performing antitumor cytotoxic activity. In line with this, in a recent report, it was found that in patients with advanced esophageal squamous cell carcinoma receiving radiotherapy combined with immunotherapy, PD-1+ CD8+ T lymphocytes exhibited higher functional and activated characteristics and had enhanced memory properties (including both EM and CM subsets) and less TEMRA cells than PD-1-CD8+ T lymphocytes [25]. Our study also revealed similar CD8+ T subset profiles for our PCa patient cohorts stratified by tumor aggressiveness.…”

Association of immune cells and the risk of esophageal cancer: A Mendelian randomization study in a East Asian population

“…[48] EC has increased expression levels of HLA-DR after immunotherapy. [49] Limited studies Lymphocyte%leukocyte in tumors have shown phocytes to be an indicator of good overall survival in a study that combined peripheral blood inflammation indices to predict survival in patients with small cell lung cancer. [50] B cells are an important subset of lymphocytes involved in humoral immunity within the adaptive immune system.…”

“…Moreover, numerous studies have indicated that immune cell phenotypes can serve as central biomarkers for immunotherapy. [ 49 , 59 , 68 – 70 ] Therefore, the 15 negative immune phenotypes we analyzed in our research may be essential biomarkers supporting immunotherapy.…”

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

“…At the advanced unresectable ESCC stage, Wei et al [ 99 ] conducted a phase Ib clinical trial of first-line treatment with RT combined with the anti-PD-1 antibody camrelizumab in patients with locally advanced ESCC who were CCRT intolerant or refused CCRT, versus ESCC patients with CCRT alone for dynamic changes in peripheral blood CD8 T-cell function and differentiation comparison. The results showed that in the RT combined with camrelizumab group, camrelizumab effectively bound to PD-1 on CD8 T cells and competed directly with PD-L1 on tumor cells, thereby reducing the suppressive effect of tumor cells on immune cells.…”

“…The results showed that in the RT combined with camrelizumab group, camrelizumab effectively bound to PD-1 on CD8 T cells and competed directly with PD-L1 on tumor cells, thereby reducing the suppressive effect of tumor cells on immune cells. Tcm subsets and Tem subsets were increased in PD-1CD8 T cells after RT plus camrelizumab treatment, whereas only Tcm subsets were increased after CCRT treatment, suggesting that RT with camrelizumab treatment may exhibit a stronger CD8 T-cell response than CCRT [ 99 ]. Based on the stronger T-cell immune response with RT in combination with camrelizumab than with CCRT, Zhang et al [ 100 ] further explored the safety and feasibility of combining CCRT with camrelizumab as a first-line treatment for patients with locally advanced ESCC.…”