NK and T-Cell Status as Well as Their Perforin Expression Is Related to Clinical Severity and Outcome in Difuse Large Cell Lymphoma.

A variable degree of immune impairment is present in lymphomas, either as a cause or a consequence of the disease. There is preliminary evidence that this immune status is related to disease control and survival. Our objective was to analyze the relationship of the immune status with the main clinical prognostic variables in DLCL. Seventeen patients with DLCL de novo were prospectively included in the study, receiving an homogenous induction treatment based on CHOP-R regimen. Median age was 60 (29–74); ECOG PS > 1 in 65%; Ann-Arbor stage > II in 53%; B-symptoms in 47%; more than one extranodal site in 47%; bulky mass present in 59%; high LDH in 65%; high beta-2-microglobulin in 56%. Levels of B, T and NK subpopulations were assessed at diagnosis by flow cytometry, including general populations as well as cytotoxicity, costimulation and adhesion phenomena. This was compared with main clinical prognostic variables included in the adjusted-IPI (a-IPI) and MD. Anderson Tumor Score (TS) by U of Mann-Whitney non parametric test or Kaplan Meier survival analysis. Worst a-IPI patients (2–3 scores) (59%) showed significant lower levels of total lymphocytes as well as of the following populations:

• General T lymphoid markers (CD2 and CD3);

• expression of adhesion molecules (CD3+CD11a+, CD4+CD11a+ and CD8+CD11a+);

• expression of costimulatory molecules (CD4+CD28+ and CD8+CD28+);

• cytotoxicity in CD56+ cells (CD56+ Perforin+).

Worst TS patients (3–4 scores) (59%) showed significant lower levels of the following populations:

• Activated or regulatory lymphoid subsets (CD3+CD25+);

• expression of costimulatory molecules (CD4+CD152+ and CD8+CD152+);

• cytotoxicity in CD56+ cells (CD56+ Perforin+).

With a median follow-up of 16 months we observed a better overall survival and progression-free survival data in patients with levels above median of CD56+ and expression of perforin by T and NK cells. We conclude that worst prognostic groups of a-IPI and TS in DLCL are associated with a worst immune status, based on T and NK immune phenomena analysis. Perforin expression by NK and T CD56+ cells was associated with outcome in DLCL.