The overall objective of this prospective observational study is to address the significant knowledge gap that exists around the impact of immune dysfunction on the development and survival from sepsis in patients with cancer. This proposal primarily focuses on establishing the transcriptomic immune profiles of sepsis patients with a background of cancer. This analysis will be complemented with in vitro functional analyses, and in addition will commence a collection of genome-wide data, including a focus on predicting white cell number and function in health. Uniquely, the investigators propose to establish a robust link between these analyses: transcriptomic, in vitro, and genome-wide, to enable them to comprehensively explore septic oncology patient 'immune phenotypes' and effectively identify novel exploitable therapeutic pathways.

To this end, this project will collect, analyse and/or sequence DNA, RNA, leukocytes and soluble materials from a cohort of oncology patients presenting to intensive care with sepsis. This cohort will include all-comers with an oncological background but will also focus on two core groups at high risk of sepsis where baseline samples can also be sought prior to major immunosuppressive events in the cancer pathway. These are:

1. Oesophageal/upper gastrointestinal (GI) cancer patients prior to systemic anticancer therapy initiation or surgery
2. Haematological malignancy patients prior to stem cell transplantation.

These sub-cohorts will provide a previously unexplored unique insight into the role of pre-existing patient transcriptomic phenotypes.

The specific aims will be to perform multi-modal parallel immune phenotyping to determine:

• The transcriptomic (RNA) phenotypes (or 'signatures') of cancer patients with sepsis

• The association of these transcriptomic phenotypes with:

  1. Leukocyte function in sepsis, as quantified by cell surface and functional assays and plasma soluble mediator content
  2. Pre-existing genomic determinants such as leukocyte numbers
  3. Severity of, and outcome from, sepsis in oncology patients

Sepsis cohort: Inclusion Criteria:

• Patients admitted to ICU with a diagnosis of sepsis as per 'Sepsis-3' definitions with a SOFA score [REF] ≥2 secondary to infection from any source
• ≥18 years of age
• Written consent from patient, personal or professional consultee, or deferred consent if none of the above available at admission

Sepsis cohort Exclusion Criteria:

• Death deemed imminent by the clinical team

Elective cohort inclusion criteria

• Patients undergoing elective major upper GI surgery (oesophago+/-gastrectomy) or stem cell transplant for haematological malignancy
• ≥18 years of age
• Written consent from patient

Elective cohort exclusion criteria

• Limitations in place regarding provision of treatment and/or organ support e.g., palliative patients

Patients who develop sepsis on ICU or require admission to ICU with sepsis will be identified and screened for enrolment by the research team at the Royal Marsden NHS Foundation Trust

Elective pre-operative upper GI surgical patients or elective stem cell transplant patients will be consented and enrolled at baseline, immediately prior to these procedures.