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Poster display session

1951 - Revealing potential immune responses (IRs) in patients with advanced colorectal cancer (aCRC) on first line chemotherapy: a prospective study of neutrophil to lymphocyte ratio, immune function and outcome.

Date

11 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Translational Research;  Colon and Rectal Cancer

Presenters

Samantha Turnbull

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

S. Turnbull1, E. West2, K. Scott2, E. Tidswell2, A. Melcher3, M. Seymour1, C. Ralph4, J. Seligmann1

Author affiliations

  • 1 Institute Of Cancer And Pathology, University of Leeds, LS9 7TF - Leeds/GB
  • 2 Section Of Infection And Immunity, Institute Of Cancer And Pathology, University of Leeds, LS9 7TF - Leeds/GB
  • 3 Translational Immunotherapy Team, The Institute of Cancer Research, SW3 6JB - London/GB
  • 4 Section Of Clinical Cancer Research, Institute Of Cancer And Pathology, University of Leeds, LS9 7TF - Leeds/GB
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Resources

Abstract 1951

Background

Neutrophil to lymphocyte ratio (NLR), a broad measure of inflammation and immune function, predicts outcome including overall survival (OS) in aCRC but the underlying mechanisms are unclear. Better understanding of IR in these patients may identify potential responders to novel immunotherapy. We investigated whether immune function correlated to NLR and how this altered during chemotherapy.

Methods

Peripheral blood was taken from 29 aCRC patients receiving 1st line chemotherapy (baseline and 6 weeks). NLR of ≥ 5 was defined as high. Immune function of peripheral blood mononuclear cells (PBMCs) was determined by NK cell activity (degranulation by CD107 expression and cytotoxic potential by 51Chromium release) against target tumour cells, T cell activity by IFN-γ ELISpot, cytokine secretion (Luminex) and immune cell activation (flow cytometry).

Results

High baseline NLR was associated with shorter OS compared to low NLR (6.6 vs. 18.8 months; HR = 3.6 [1.25 to 10.35] p = 0.0024). High NLR also correlated with a depressed IR, including decreased cytolytic activity of PBMCs (p = 0.046), NK cell degranulation at baseline and decreased levels of certain immune stimulatory cytokines. Low baseline NLR correlated with increased T cell activity against tumour-associated carcinoembryonic antigen (CEA) after 6 weeks of chemotherapy. Higher cytotoxic activity of PBMCs against target tumour cells at baseline (seen in the majority of patients with NLR

Conclusions

This study supports the poor prognosis of a high baseline NLR in aCRC and demonstrates its association with an attenuated IR. Chemotherapy can partially reverse this phenomenon, potentially enhancing anti-tumour immunity. If chemotherapy leads to a more effective anti-tumour IR, sequential immunotherapy could exploit this.

Clinical trial identification

Legal entity responsible for the study

University of Leeds

Funding

Cancer Research UK, Yorkshire Cancer Research

Disclosure

All authors have declared no conflicts of interest.

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