The immune modulation effects of gemcitabine plus cisplatin induction chemotherapy in nasopharyngeal carcinoma

Xiao-Min Li, Xiao-Min Zhang, Jun-Yan Li, Ning Jiang, Lei Chen, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Guan-Qun Zhou, Ying-Qin Li, Na Liu, Yuan Zhang, Jun Ma, Xiao-Min Li, Xiao-Min Zhang, Jun-Yan Li, Ning Jiang, Lei Chen, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Guan-Qun Zhou, Ying-Qin Li, Na Liu, Yuan Zhang, Jun Ma

Abstract

Background: Studies are trying to add immunotherapy to gemcitabine and cisplatin (GP) induction chemotherapy, the standard therapy, in nasopharyngeal carcinoma (NPC) patients with locoregionally advanced disease. However, how the immune system responds to GP remains unknown.

Method: We examined the dynamic changes of circulating immune cells and plasma cytokines in NPC patients administered with GP.

Result: After GP administration, immunosuppressive myeloid cells, including CD11b+CD14+ monocytes, CD33+ myeloid cells, CD33+CD11+ myeloid cells, total MDSCs (CD33+CD11+HLA-DR-/low), monocytic MDSCs, and granulocytic MDSCs decreased significantly. The regulatory T cells and B cells, two important suppressive lymphocyte subpopulations, also decreased. On the other hand, the levels of CD3+ T cells, total B cells, central memory CD4+ T cells, and pro-inflammatory cytokines (including Interleukin [IL]-1β, IL-6, IL-2, IL-5, and IL-8) increased significantly after GP administration. Besides, GP chemotherapy did not weaken the cytotoxic activity and proliferative capacity of T cells.

Conclusion: Our results showed the immune modulation effect of GP induction chemotherapy in locoregionally advanced NPC, providing a solid basis for its combination with immunotherapy.

Trial registration: ClinicalTrials.gov NCT03984357 NCT03619824.

Keywords: cisplatin; combination therapy; gemcitabine; immune modulation; nasopharyngeal carcinoma.

Conflict of interest statement

There is no competition of interest.

© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
The influence of gemcitabine and cisplatin chemotherapy (GP) on myeloid cells. The dynamic changes of CD11b+CD14+ monocytes (A), CD33+ common myeloid cells (B), CD33+CD11b+ myeloid cells (C), myeloid‐derived suppressor cells (CD33+CD11b+HLA‐DR−/low, MDSCs) (D), CD14+ monocytic MDSCs (E), and CD15+ granulocytic MDSCs (F) in 39 patients during GP treatment. (*P <0.05, **P <0.01, ***P <0.001, ns: not statistically significant)
FIGURE 2
FIGURE 2
The effect of GP on T‐cell subsets. The dynamic changes of CD3+ cells (A), CD4+ T cell (B), CD8+ T cells (C), regulatory T cells (CD3+CD4+CD25+Foxp3+, Tregs) (D), conventional T cells (CD4+CD25−) (E), CD3+/Tregs ratios (F) in 39 patients during GP treatment. (*P <0.05, ***P <0.001, ns: not statistically significant)
FIGURE 3
FIGURE 3
The effect of GP treatment on CD4+/CD8+ T‐cell subtypes. The dynamic changes of CD3+CD4+CD45RA+CCR7+naïve CD4+ T cells (A), CD3+CD4+CD45RA+CCR7− terminally differentiated CD4+ T cells (B), CD3+CD4+CD45RA‐CCR7+ central memory CD4+ T cells (C), CD3+CD4+CD45RA‐CCR7− effector memory CD4+ T cells (D), CD3+CD8+CD45RA+CCR7+ naïve CD8+ T cells (E), CD3+CD8+CD45RA+CCR7− terminally differentiated CD8+ T cells (F), CD3+CD8+CD45RA‐CCR7+ central memory CD8+ T cells (G), and CD3+CD8+CD45RA‐CCR7− effector memory CD8+ T cells (H) in 13 NPC patients during GP treatment. (*P <0.05, ns: not statistically significant)
FIGURE 4
FIGURE 4
The influence of GP treatment on T‐cell function and lymphocyte proliferation. A‐D. The dynamic changes of granzyme B or perforin positive CD3+ T cells and CD8+ T cells in 13 NPC patients during GP treatment. E. The dynamic changes in the proliferative capacity of the lymphocytes of seven patients during GP treatment. (ns: not statistically significant)
FIGURE 5
FIGURE 5
The effect of GP treatment on B cells. A‐B. The dynamic changes in the levels of CD19+ B cells and CD19+CD38+CD24+ regulatory B cells in 39 patients during GP treatment. (***P <0.001, ns: not statistically significant)
FIGURE 6
FIGURE 6
The effect of GP on immunomodulatory plasma proteins. The dynamic changes in the levels of TNFα, GM‐CSF, IL‐1b, IL‐2, IL‐5, IL‐6, IL‐8, VEGF, IL‐10, IL‐4, and TGF‐β1 (A‐K) in 39 patients during GP treatment. (*P <0.05, ***P <0.001, ns: not statistically significant)

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