Abstract 1842
Background
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.
Methods
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.
Results
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).
Conclusions
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
Editorial acknowledgement
Legal entity responsible for the study
Saitama Medical University International Medical Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4085 - A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-601 in Patients with Advanced Solid Tumors
Presenter: Anthony Tolcher
Session: Poster Display session 1
Resources:
Abstract
1054 - Safety, efficacy, and pharmacokinetic (PK) profile of cosibelimab, an anti‐PD‐L1 antibody, in patients (pts) with advanced cancers
Presenter: Philip Clingan
Session: Poster Display session 1
Resources:
Abstract
4264 - A Phase I study of tinostamustine in patients (pts) with advanced solid tumours
Presenter: Alain Mita
Session: Poster Display session 1
Resources:
Abstract
3811 - Lurbinectedin (LUR) in combination with Irinotecan (IRI) in patients (pts) with advanced solid tumors
Presenter: Santiago Ponce Aix
Session: Poster Display session 1
Resources:
Abstract
1311 - A phase I study of varlitinib (VAR; ASLAN001) an oral pan-HER tyrosine kinase inhibitor (TKI) combined with mFOLFIRI chemotherapy in advanced solid tumors
Presenter: Aaron Tan
Session: Poster Display session 1
Resources:
Abstract
3482 - Phase I study of lapatinib and trametinib in patients with KRAS mutant colorectal, non-small cell lung and pancreatic cancer
Presenter: Sanne Huijberts
Session: Poster Display session 1
Resources:
Abstract
4749 - Pharmacokinetic (PK) and updated survival data from the Canadian Cancer Trials Group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy
Presenter: Desiree Hao
Session: Poster Display session 1
Resources:
Abstract
4530 - A Phase 2a clinical trial combining ALRN-6924 and palbociclib for the treatment of patients with tumors harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplification
Presenter: Funda Meric-Bernstam
Session: Poster Display session 1
Resources:
Abstract
4280 - Updated Efficacy and Safety of Entrectinib in Patients with NTRK Fusion-Positive Tumors: Integrated Analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Christian Rolfo
Session: Poster Display session 1
Resources:
Abstract
6144 - An international randomized cross-over bio-equivalence study of oral paclitaxel + HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumors
Presenter: Christopher Jackson
Session: Poster Display session 1
Resources:
Abstract