This is an exploratory study embedded in the Phase Ib/II clinical trial of CD3 x 4-1BB x CD19 x PD-L1 tetra-specific T cell engager GNC-038 in relapsed and refractory diffuse large B-cell lymphoma initiated by the corresponding pharmaceutical company. By measuring immune cell components and their functional phenotypes in peripheral blood and tumor tissues before and after the subject's medication, this study aims to identify key immune cell populations and immune molecules which play an important role in resistance to GNC-038 treatment, so as to optimize drug design and develop combination therapies to improve treatment efficacy.

Inclusion Criteria:

For Group 1, the selection criteria are firstly concordant with those of the corresponding clinical trial. On this basis, additional selection criteria for this study are:

• Lymph node lesions with long diameter ≥ 2cm.
• Subjects have the ability and willingness to follow the visit, biosample collection and other research-related processes prescribed by the research program and to sign informed consent forms.

For Group 2, the selection criteria are:

• The subject is able to understand the informed consent form, and voluntarily participates and signs the informed consent form;
• Age between 18 and 80;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 points.

Exclusion Criteria:

For Group 1, the exclusion criteria are totally concordant with those of the corresponding clinical trial. There is no additional exclusion criteria for this study.

For Group 2, the exclusion criteria are:

• History of past or present malignant diseases;
• Patients with active autoimmune diseases, or patients with a history of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's granulomatosis, polyvascular inflammation granuloma, Grave's disease, rheumatoid arthritis, pituitary inflammation, ophthalmic pigmentitis, autoimmune hepatitis, systemic sclerosis, Hashimoto thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain- Barre syndrome), etc.;
• Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection (HBsAg-positive or HBcAb-positive, HBV-DNA test positive), hepatitis C virus infection (HCV antibody-positive and HCV-RNA test positive), EB virus infection (EBV-DNA test positive), cytomegalovirus infection (CMV-DNA test positive) or herpes simplex virus infection (HSV-DNA test positive);
• Pregnant or nursing women;
• Previous organ transplants or allogeneic hematopoietic stem cell transplants;
• Under treatment of immunosuppressants, including but not limited to cyclosporine, tacrolimus, corticosteroids, etc., within 1 month prior to sampling;
• Fever (temperature >37.5 ℃) within 1 month prior to sampling, or using antibiotics due to respiratory, gastrointestinal, urinary tract infections, etc.;
• Other situations in which the researchers consider it inappropriate for the patient to participate in this study.

This study plans to include 10 subjects enrolled in the GNC-038 Phase Ib/II clinical trial in Ruijin Hospital. It also plans to include five patients who have tonsillectomy in Ruijin Hosptial due to obstructive sleep apnea and hyponea syndrome as the control group.