89P - Immune homeostasis mediators and disease progression in chemotherapy-naïve and neoadjuvant chemotherapy treated gastric cancer patients

Background

Current treatment strategies have improved gastric cancer (GC) patient survival yet disease progression risks remain considerable. Attention is directed to immune homeostasis mediators as indicators of therapy impact. Study aimed at investigating immunomodulatory cells & cytokines profiles in chemotherapy-naïve and Neoadjuvant chemotherapy (NACT) treated GC patients.

Methods

Prospective cohorts of 46 GC patients scheduled for surgical tumor excision first (CTn; n=18) or following NACT treatment (NACT; n=28) were included. NACT were grouped according to Mandard’s criteria into Responders (R;TRG1- 3;n=14) and Non-Responders(NR;TRG4-5;n=14). Peripheral blood samples for PBMCs and serum isolation were collected before surgery. Characterization of immune populations (cytotoxic CD3+CD8+ T-cells, CD4+FOXP3+ T-regs, CD3- CD16+CD56mid+ NKcells, CD3+CD16+ NKTcells & CD14+CD16-/CD14+CD16+/CD14-CD16+monocytes) & serum cytokines (IL-2, IL-4, IL-6, IL- 10, TNFa, IL-17a; by Cytometric Bead Arrays) was performed with FACS.

Results

NACT patient profiles revealed immune status differences between R and NR patients. R were defined by upregulated Tregs (p=0.016 vs NR), antitumor NKcells and intermediate (CD14+CD16+) monocytes (p=0.031 vs NR) and a concomitant profile of moderate increase of cytokines IL2, IL4, IL6 and IL10. In contrast, NR were characterized by increased classical (CD14+CD16-) monocytes, cytotoxic Tcells and NKTcells. NR also showed a reduction of IL2 and anti-inflammatory cytokines IL10 and IL4. CTn patients exhibited a similar to NR immunoprofile of increased cytotoxic populations, but also relatively increased Tregs, whilst cytokine patterns revealed predominance of pro- inflammatory TNFa and elevated IL4 and IL17a.

Conclusions

Responders were characterized by abundance of contributing to immunocompetence immune cells & antitumor acting cytokines whilst tumour progression in CTn & chemoresistant patients correlated with predominance of cytotoxic immunosurveilance populations & deprivation of immunoregulatory cytokines. Evidence highlights the immunomodulators profilling potential towards personalizing GC patient management.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

National and Kapodistrian University of Athens, Greece.

Funding

ERAPerMed 2019-275 (GRAMMY). ERAPerMed - Joint Transnational Call for Proposals (2019) for “Personalised Medicine: Multidisciplinary Research Towards Implementation”.

Disclosure

All authors have declared no conflicts of interest.