Despite impressive outcomes in selected patients, significant heterogeneity in clinical response to CAR-T cell therapy remains. The gut microbiome (GM) has recently emerged as one of the key modifiable factors of prognosis and response to treatment in cancer patients, with high-diversity profiles rich in health-associated taxa while poor in pathobionts generally associated with better response and longer survival. Currently, it is unknown if GM also modulates anti-tumor responses to CAR-T cells and related toxicities in lymphomas.

Inclusion Criteria:

1. Age ≥18 years.
2. Patients affected by histologically confirmed DLBCL.
3. Patients amenable for CAR-T cell therapy as for clinical approved indication (commercial products).
4. Patients must provide written informed consent.

Exclusion Criteria:

1. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.
2. Concurrent second malignancy.

Up to 90 relapsed/refractory diffuse large B-cell lymphoma adult (≥18 years) patients undergoing CAR-T cell therapy will be enrolled over 3 years, treated and followed up with fecal sample collection until 18 months after CAR-T cell infusion.