[Nat Med] Tumor immune microenvironment plays a decisive role in car T treatment for large B-cell lymphoma

CAR T

Immune microenvironment

Currently, CAR T-cell therapy benefits most in patients with aggressive B-cell non-Hodgkin lymphoma (called diffuse large B-cell lymphoma (DLBCL),, although about 60% of patients with DLBCL will eventually progress

There have been many studies on the mechanisms of CAR T resistance, such as tumor CD19 deletion (called 'antigen escape'), but the reasons for treatment failure are often unclear and there are not enough biomarkers to predict the outcome

In the recent Nature Medicine study, Scholler et al.

In their study, Scholler et al.

This study shows a novel and impressively strong correlation between TME and clinical outcomes

In addition to CAR T cell efficacy, pretreatment TME can also predict the safety of CAR T cell therapy: intratumoral regulatory T cells are associated with lower rates of severe neurotoxicity after treatment and do not affect clinical outcomes (see figure below for immune microenvironmental factors that affect clinical outcomes).

For CAR T, biomarkers that predict outcome before or shortly after treatment can be designed are important because they may inform future trials of high-risk patients with CAR T combination regimens

Scholler et al.

According to this study, there is a lack of correlation between the traditional molecular subtype of DLBCL and the post-CAR T outcome, which is consistent with the results of key CAR T clinical studies, and it is interesting

It is worth noting that some biomarkers associated with clinical efficacy may also be the root cause of their efficacy in turn, so it is possible to make the efficacy better

With the integration of CAR T cell therapy into early DLBCL treatment, its latest approval in multiple myeloma, and the study of novel CAR T cells in solid tumors and hematologic malignancies, the number of patients receiving CAR T cell therapy will increase

： ，