To detect the difference of PD-L1 and miRNA expression profiles of exosomes in NSCLC patients before and after immunotherapy, and to explore the potential of plasma exosomes PD-L1 and miRNAs as biomarkers to predict the therapeutic effect of NSCLC on anti-PD-1 / PD-L1.

Inclusion Criteria:

1. Sign informed consent.
2. The age is greater than or equal to 18 years old.
3. There is at least one measurable focus according to the RECIST 1.1 standard
4. EGFR / ALK detection is not needed in patients with metastatic (stage IV) EGFR / ALK wild-type NSCLC confirmed by histology or cytology and in patients with squamous cell carcinoma.
5. Cohort 1: patients receiving anti-PD-1 (pabolizumab) treatment combined with chemotherapy as the first-line treatment Cohort 2: patients who received the second-line treatment of anti-PD-1 single drug (nafulizumab) for the progress of disease after chemotherapy with platinum containing dual drugs
6. ECoG score is 0, 1 or 2.
7. No serious blood system, heart, lung, liver and kidney dysfunction and immune deficiency.
8. Hemoglobin (HB) ≥ 9g / dl; leukocyte (WBC) ≥ 3 * 109 / L; neutrophil (ANC) ≥ 1.5 * 109 / L; platelet (PLT) ≥ 75 * 109 / L.
9. Men or women of childbearing age are willing to take contraceptive measures in the experiment.
10. Estimated survival time ≥ 3 months.

Exclusion Criteria:

1. Histologically, small cell and non-small cell mixed lung cancer.

2. Pregnant or nursing women.

3. Any unresponsive > CTCAE Level 2 toxicity caused by past anti-tumor treatment

4. Serum creatinine clearance < 30 ml / min (calculated by Cockcroft Gault formula)

5. Liver dysfunction, defined as:

   1. Serum (total) bilirubin > 1.5 × upper limit of normal value (ULN)
   2. Serum AST / SGOT or ALT / SGPT > 2.5 × ULN (liver metastasis > 5 × ULN)
   3. Alkaline phosphatase level > 2.5 × ULN (liver metastasis > 5 × ULN, or bone) at baseline Transfer patients > 10 × ULN)

6. Have a history of uncontrollable or symptomatic angina, arrhythmia or congestive heart failure.

7. Symptomatic brain metastasis or meningeal metastasis.

8. In the past 5 years, she has had or is suffering from other histological types of malignant tumors, except for cervical carcinoma in situ and fully treated skin basal cell carcinoma or squamous cell carcinoma.

9. Have active, or have had and may recur autoimmune diseases. However, subjects with type I diabetes, hypothyroidism requiring hormone replacement therapy only, skin diseases without systemic treatment (such as vitiligo, psoriasis or alopecia), or no relapse without external triggers are expected.

10. Diagnosis of immunodeficiency or systemic hormone therapy (e.g., hormone therapy equivalent to > 10 mg prednisone per day) or any other form of immunosuppressive therapy within 7 days before the first administration.

11. Patients with known history of human immunodeficiency virus (HIV) infection and / or acquired immunodeficiency syndrome. Subjects with active hepatitis B or active hepatitis C

12. Grade 2 pneumonia caused by radiotherapy and chemotherapy (grade 2 pneumonia without systemic hormone treatment recovers to grade 1 or below within 14 days, if the researcher judges that there is no risk of recurrence, it can be included in the group for screening).

13. Have interstitial lung disease and the disease has symptoms.

14. During the study period, radiotherapy is planned for the target focus.

15. Plan to use other anti-tumor therapy during the study period.

16. Patients with serious or uncontrolled systemic diseases who are not suitable for the study or may affect the compliance of the other party's case. Subjects' complications or other conditions may affect compliance with the protocol or may not be suitable for the study.