The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy - results from the AGITG DOCTOR trial and the cancer evolution biobank.

Autor:	Lonie JM; Surgical Oncology Group, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia., Brosda S; Surgical Oncology Group, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia., Bonazzi VF; Surgical Oncology Group, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia., Aoude LG; Surgical Oncology Group, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia., Patel K; Surgical Oncology Group, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia., Brown I; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Envoi Specialist Pathologists, Brisbane, QLD, Australia.; Department of Pathology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia., Sharma S; Medlab Pathology, Sydney, NSW, Australia.; Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Lampe G; Department of Anatomical Pathology, Central Laboratory Pathology Queensland, Brisbane, QLD, Australia., Addala V; Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Koufariotis LT; Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Wood S; Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Waddell N; Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Dolcetti R; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Translational and Clinical Immunotherapy, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.; Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia., Barbour AP; Surgical Oncology Group, Frazer Institute, The University of Queensland, Brisbane, QLD, Australia.; Department of Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Oct 12; Vol. 14, pp. 1220129. Date of Electronic Publication: 2023 Oct 12 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1220129
Abstrakt:	A plateau in treatment effect can be seen for the current 'one-size-fits-all' approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality. This study included 107 patients; 68 patients were enrolled in the Australian Gastro-Intestinal Trials Group sponsored DOCTOR Trial, and 38 patients were included from the Cancer Evolution Biobank. Matched pre-treatment and post-treatment tumour biopsies were used to perform multi-modality analysis of the OAC TME including NanoString mRNA expression analysis, multiplex and single colour immunohistochemistry (IHC), and peripheral blood mononuclear cell analysis of tumour-antigen specific T cell responses. Patients with the best clinicopathological outcomes and survival had an immune-inflamed TME enriched with anti-tumour immune cells and pathways. Those with the worst survival showed a myeloid T regulatory cell enriched TME, with decreased CD8 + cell infiltration and increased pro-tumour immune cells. Multiplex IHC analysis identified that high intra-tumoural infiltration of CD8 + cells, and low infiltration with CD163 + cells was associated with improved survival. High tumour core CD8 + T cell infiltration, and a low tumour margin infiltration of CD163 + cells was also associated with improved survival. nCRT showed improved survival compared with nCT for patients with low CD8 + , or high CD163 + cell infiltration. Poly-functional T cell responses were seen with tumour-antigen specific T cells. Overall, our study supports the development of personalised therapeutic approaches based on the immune microenvironment in OAC. Patients with an immune-inflamed TME show favourable outcomes regardless of treatment modality. However, in those with an immunosuppressed TME with CD163 + cell infiltration, treatment with nCRT can improve outcomes. Our findings support previous studies into the TME of OAC and with more research, immune based biomarker selection of treatment modality may lead in improved outcomes in this deadly disease. Competing Interests: NW is a founder of genomiQa Pty Ltd and members of its Board. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Lonie, Brosda, Bonazzi, Aoude, Patel, Brown, Sharma, Lampe, Addala, Koufariotis, Wood, Waddell, Dolcetti and Barbour.)
Databáze:	MEDLINE
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