Patients with diffuse large B-cell lymphoma (DLBCL) who have a low proportion of T-cells in the tumor microenvironment show mechanisms of immune escape and have poor survival when treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydroxydaunorubicin, Oncovin, and prednisone), found a new study published in the journal Haematologica.
It was already known that the tumor microenvironment held clues about the prognosis of DLBCL.
Read more about the prognosis of DLBCL
In the present study, a team of researchers led by Alex F. Herrera, MD, from the Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, in Duarte, California, investigated the ratios of T-cell subsets, macrophages, and natural killer cells in 57 patients with DLBCL treated with R-CHOP.
The results showed that a very low proportion of CD3+ T-cells and a low proportion of CD4+PD1+ and CD8+PD1+ T-cells were associated with poor survival in these patients compared to a high proportion of T-cells.
Moreover, low expression of mucin-domain containing 3 (TIM3) and programmed cell death 1 (PD1) proteins on immune cells was also associated with poor prognosis.
The researchers validated these findings in an additional 53 patients with DLBCL as well as gene expression profiling data from 351 patients.
Finally, the team showed that patients who had a mutation in genes such as B2M, HLA I, and/or HLA II, which led to a loss of protein expression on the tumor cells, also had a low ratio of T-cells. This, the authors of the study said, supports the idea that the lack of these proteins allows immune escape.
“In conclusion, our findings demonstrate that analysis of the [tumor microinveronment] can play an important prognostic role in DLBCL,” they wrote. “These findings further our understanding of the role of the [tumor microenvironmenet] in DLBCL and the mechanisms that tumor cells utilize for immune escape,” the study authors noted.
Reference
Song JY, Nwangwu M, He TF, et al. Low T-cell proportion in the tumor microenvironment is associated with immune escape and poor survival in diffuse large B-cell lymphoma. Haematologica. Published online January 12, 2023. doi:10.3324/haematol.2022.282265