Abstract 1480P
Background
Tumor microenvironment plays a crucial role in cancer development and tumor-associated macrophages (TAMs) are emerging as key players. Nevertheless, TAMs role in advanced Gastric Cancer (GC) need to be further clarified. The inability of lymphocytes to reach tumor cells is an important mechanism of treatment resistance and cancer exclusion of CD8 T cells is correlated with a poor clinical outcome. Macrophages contribute to lymphocyte trapping by long-lasting interactions with CD8 T cells that causes immunosuppression and poor outcome. Our work aims at assessing the relation between macrophages and lymphocytes in fresh tumor biopsies and normal mucosa from patient diagnosed with advanced GC.
Methods
In a multicentric prospective cohort enrolling patients with advanced GC, fresh biopsies from peritumoral mucosa and gastric tumor were collected from July 2019. After tissue digestion, cells were isolated and a Flow cytometry analysis (FACs) was performed by BD LSRFortessa cytometer using a customized panel to study immune cells population in the tumor microenvironment. Pathological evaluation, immunohistochemistry for PD-L1 and the analysis of Tumor infiltrating lymphocytes (TILs) were performed accordingly in all samples. For transcriptomic analyses, RNA extraction was carried out according to the manufacturer (Qiagen®).
Results
So far, 16 tumor samples and matched normal mucosae met the clinical and quality sample criteria to be included in this study. Transcriptomic analyses were performed to characterize immune expression profile in tumor samples and normal mucosa. All samples were analyzed by FACs. The estimation of TIL by both, FACs and IHC, were significantly correlated (p=0.03). Interestingly, it was found an inverse correlation between the number of M2-Macrophages and Lymphocytes (Pearson’s product-moment correlation of -0.5 (p= 0.021)). These results highlight a potential immunosuppressive role of M2 macrophages in our cohort.
Conclusions
M2-Macrophages determined immunosuppression and cold immune phenotype in our cohort of GC. Further investigations are needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was supported by grants from the Carlos III Health Institute (PI18/01508 to TF; PI15/02180 and PI18/01909 to AC). MC is supported by a pre-doctoral grant from the Spanish Cancer Association (AECC), Spain. VG was supported by the ESMO 2014 fellowship program and by a Rio Hortega contract CM18/00241 from the Carlos III Health Institute. TF is supported by Joan Rodes contract 17/00026 from the Carlos III Health Institute.
Disclosure
A. Cervantes: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Servier; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): Astelas; Advisory/Consultancy: Pierre Fabre; Speaker Bureau/Expert testimony: Genentech; Speaker Bureau/Expert testimony: Angem; Research grant/Funding (institution): Fibrogen; Research grant/Funding (institution): Amcure; Research grant/Funding (institution): Sierra Oncology; Research grant/Funding (institution): Astra Zeneca; Research grant/Funding (institution): Medimmune; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MSD; Speaker Bureau/Expert testimony: Foundation Medicine. All other authors have declared no conflicts of interest.