16P - The role of systemic immunity in locally advanced gastric cancer patients treated with neoadjuvant chemotherapy

Background

Neoadjuvant chemotherapy (NCT), followed by surgery represents the standard of care for locally advanced gastric cancer (GC), but efficacy of such treatments is still limited for many patients (pts). Aim of this study was to investigate the role of systemic immunity in therapy response in this subset of pts.

Methods

A prospective cohort of 15 GC pts who received NCT was considered. Response to NCT was evaluated by tumor regression grade. Blood samples were collected at 4 different timepoints (preNCT, postNCT, post-surgery and post-adjuvant). Immune phenotype screening of peripheral blood mononuclear cells (PBMCs) was performed by multiparametric cytometry. IL2, IL4, IL6, IL10, IL17a, and TNFα evaluation on serum samples was conducted by cytometric bead array.

Results

Among pts, 33% showed a complete response (CR) whereas 20% and 47% only partial (PR) or no-response (NR), respectively. Cytometric immunophenotyping revealed that non-classical monocytes (CD14+-CD16++) were elevated in NR with a tendency to increase in the course of therapy whilst showing an opposite trend in CR (p=0.006). A time-dependent increase of terminal effector T cells (Te) (CD4+CD45RA+CCR7-) was associated with NR (p=0.015), whereas activated Te (CD4+CD45RA+CCR7-CD27+CD28+) and effector memory T cells (Tem) (CD4+CD45RA-CCR7-) showed higher basal levels in CR pts and a trend to increase during treatment (p=0.026 & p=0.007, respectively). Immunomodulators profiles revealed the signficant association of higher TNFα levels detected at baseline with NR (p=0.034), in line with TNFa’s strong correlation with ypT stage (p=0.003). Interestingly, TNFa levels showed also a significant positive correlation with Te (preNCT: p=0.01) and CD8+CTLA4+ lymphocytes (preNCT: p=0.01 & postNCT: p<0.001), the latter standing out also as the immunopopulation associated with NR (p=0.028).

Conclusions

These preliminary results indicate a role for systemic immunity in NCT response in GC pts. TNFα and immunosuppressive subpopulations correlated to poor response. By contrast, activated Te and Tem cells emerged as contributors to therapy response. Evidence showcases the potential of monitoring peripheral immune biomarkers in predicting therapy response.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”.

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.