Abstract 89P
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.
Resources from the same session
20P - Effects of <italic>Apis dorsata</italic> honey on the expression of selected CYP450, pro-apoptotic, and anti-apoptotic genes during induced cytotoxicity in cyclophosphamide-treated human lung carcinoma (A549) cells
Presenter: Jose Kenneth Narag
Session: Cocktail & Poster Display session
Resources:
Abstract
21P - Hsa_circ_0009061 inhibits the progression of bladder cancer through the miR-889-3p/CPEB3 axis
Presenter: Minkang Wu
Session: Cocktail & Poster Display session
Resources:
Abstract
22P - Exploring exportin-1 as a therapeutic vulnerability in lung squamous cell carcinoma
Presenter: Vidushi Durani
Session: Cocktail & Poster Display session
Resources:
Abstract
23P - Identification of HPSE as potential novel therapeutic target for lung adenocarcinoma patients
Presenter: Samuel Doré
Session: Cocktail & Poster Display session
Resources:
Abstract
24P - High-throughput plasma proteomics profiling in early breast cancer
Presenter: Isabella Lombardo
Session: Cocktail & Poster Display session
Resources:
Abstract
25P - Immunohistochemical analysis of ROR1 and BMI-1 expression in luminal breast cancer
Presenter: Sergey Vtorushin
Session: Cocktail & Poster Display session
Resources:
Abstract
26P - Associations between cancer stem cells (CSC) markers and androgen (AR) and estrogen (ER) receptors expression in prostate cancer (PCa)
Presenter: Marina Puchinskaya
Session: Cocktail & Poster Display session
Resources:
Abstract
27P - Proteomic profiling reveals organ-specific differences in metastases and identifies potential biomarkers for recurrence risk in localized colon cancer
Presenter: Blanca García-Micó
Session: Cocktail & Poster Display session
Resources:
Abstract
28P - Collagen-activated signalling pathway is significantly hypermethylated in high-grade serous ovarian cancer (HGSOC) patients treated with platinum-containing neoadjuvant chemotherapy (NACT)
Presenter: Jose Alejandro Perez Fidalgo
Session: Cocktail & Poster Display session
Resources:
Abstract
29P - Quantitative tissue analysis reveal adenylate kinase 2 protein signatures: Therapeutic target for meningioma
Presenter: Rashmi Rana
Session: Cocktail & Poster Display session
Resources:
Abstract