Immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (NSCLC) and have become one of standard therapy. It was demonstrated that nivolumab therapy for resectable NSCLC patients prior to surgery resulted in major pathological responses in 40% of the patients. On the other hand, adjuvant nivolumab therapy for melanoma resulted in longer recurrence-free survivals. Thus, it is still uncertain which host immunological status is appropriate for ICI therapy, before or after surgery. In this study, we examined the peripheral blood, and tumor tissues to elucidate immunological impact of surgery in NSCLC patients.
The present study comprised of 20 surgically resectable early (stage I, II, or IIIA) NSCLC patients in Saitama Medical University International Medical Center. Peripheral blood samples were collected before and after surgical resection of NSCLC. PBMCs were analyzed with LSR FortessaTM.
Interestingly, more effector memory (EM) CCR7-CD45RA- CD8+ T cells and CD62Llow CD4+ T cells were observed in early stage NSCLC patients, compared with stage IV NSCLC patients. Significant decrease of the percentages of EM CD8+ T cells (P = 0.0045) and CD62Llow CD4+ T cells (P < 0.0001) were detected after surgical removal of cancer. In contrast, central memory (CM) CCR7+CD45RA- CD8+ T cells significantly increased (P = 0.0037). It is likely that the decrease of EM CD8+ T cells and CD62Llow CD4+ T cells reflected conversion of EM T cells to CM T cells due to disappearance of cancer antigens, because the decrease was not observed in the patients of incomplete resection. PD-1 expression on both CD8+ and CD4+ T cells was up-regulated after surgery. The percentages of myeloid derived suppressor cells (MDSC) (P < 0.0001) increased and natural killer cells (NK) decreased (P = 0.0001).
After surgical removal of lung cancer, EM type T cells were converted to CM type T cells. It seems that surgery may have negative influence for innate immunity. Because PD-1 blockade therapy only activates primed effector T cells, the immunological status before surgery seems more appropriate for ICI therapy.
Clinical trial identification
Legal entity responsible for the study
Saitama Medical University International Medical Center.
Has not received any funding.
All authors have declared no conflicts of interest.