An Experimental Medicine Clinical Study to Compare Peripheral Immune System From Subjects Without Cancer Diagnosis and Patients With Solid Tumours.

• INCLUSION CRITERIA FOR ALL PARTICIPANTS (PATIENTS WITH CANCER AND HEALTHY VOLUNTEERS)

1. The participating subjects are able to provide signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
2. Men and women must be of 45 to 70 years of age on the day the consent is signed. Non-cancer subjects should be age matched by +/- 5 years with the cancer patient population.
3. Subject must have a Negative HIV
4. Adequate hematological parameters as assessed by laboratory tests within 21 days for cancer patients and 96 hours for healthy volunteers prior to the day of blood withdrawal:

   1. Absolute Neutrophil Count (ANC) ≥1500/µL
   2. Platelet count ≥100 000/µL, criteria must be met without transfusion and thrombopoietin for at least two weeks prior to the day of blood withdrawal
   3. Hemoglobin ≥9g/dL, criteria must be met without transfusion and erythropoietin for at least two weeks prior to the day of blood withdrawal
5. Physical ability to tolerate a 60 ml-blood sampling.
6. Subjects affiliated to a social security regimen or beneficiary of the same according to local requirements

   • INCLUSION CRITERIA FOR CANCER PATIENTS ONLY
7. Patients currently off treatment with histologically or cytologically confirmed following diagnosis:

   * Cohort 1: Unresectable, locally advanced or metastatic Non-Small Cell Lung cancer after at least 1 or 2 standard treatment lines (including 1 line with Immune Checkpoint Inhibitor) and being scheduled for a new anti-cancer treatment after progression
   * Cohort 2: Unresectable, locally advanced or metastatic Colorectal cancer after at least 2 treatment lines
   * Cohort 3: Unresectable, locally advanced or metastatic Pancreatic cancer after at least 1 or 2 treatment lines
   * Cohort 4: Unresectable, locally advanced or metastatic Liver cancer before or after at least 1 treatment line
   * Cohort 5: Unresectable, locally advanced or metastatic Gastric cancer after at least 1 treatment line Unresectable, locally advanced or metastatic Cholangiocarcinoma before or after at least 1 treatment line

     * NON-INCLUSION CRITERIA FOR ALL PARTICIPANTS (PATIENTS WITH CANCER AND HEALTHY VOLUNTEERS)
8. Pregnant women
9. Subjects with an active autoimmune disease that is currently requiring systemic anti-inflammatory treatment such as disease-modifying anti-rheumatic drugs \[DMARDs\], steroids, or immunosuppressants), except vitiligo, alopecia areata, asthma/atopy and psoriasis treated and controlled by topical therapies. Patients with auto-immune endocrinopathies that are well treated by replacement hormones therapies (e.g. thyroxine, insulin, physiological steroids for adrenal or pituitary) are allowed. Patients with a history of immune related adverse events (irAEs) from a previous line of treatment must have resolved their irAEs to a grade ≤1 and have stopped any immunosuppressive/steroid therapy
10. Subjects with any serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever \>38ºC within 2 weeks prior to blood withdrawal.
11. Subjects who have had a laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) test within 60 days prior to blood withdrawal.
12. Patients seropositive for and with evidence of active viral infection with hepatitis B virus (HBV). Patients who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA negative are eligible.

    1. Patients who had HBV but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible.
    2. Patients who are seropositive because of HBV vaccine are eligible. Note: a quantitative PCR test result of \< 10 IU/mL is equivalent to being undetected (negative). Subject with no available results for hepatitis B virus (HBV) are eligible.
13. Patients seropositive for and with active viral infection with hepatitis C virus (HCV). Patients who had HCV but have received an antiviral treatment and show no detectable HCV viral DNA for 6 months are eligible.

    Note: a quantitative PCR test result of \< 10 IU/mL is equivalent to being undetected (negative). Subject with no available results for hepatitis C virus (HCV) are eligible.
14. Subjects who have received prior systemic anticancer therapy, definitive radiotherapy (palliative radiation therapy is allowed), or other investigational agents or device within 14 days prior to the day of blood withdrawal (or 5 half-lives of the therapeutic agents whatever the shortest). Patients who are in the screening period of an investigational study may participate if they are currently off-treatment. Patients who have entered the follow-up period of an investigational study may participate if it has been 2 weeks after the last dose of the previous investigational agent.
15. Subjects who have received approved or investigational immunomodulators (targeting any immune cell types, such as anti-CTLA-4, anti-PD-L1, any immunomodulatory in a clinical trial) in the past 6 months (except for the NSCLC cohort).
16. Subjects who have not recovered from the effects of a major surgery.
17. Subject under guardianship, curatorship or safeguard of justice
18. Subjects who have received a vaccine within 60 days prior to blood withdrawal.