# Altered dynamics of T cell subsets in peripheral blood impacts disease progression in newly diagnosed multiple myeloma

## TL;DR

This study shows that T cell imbalances in newly diagnosed multiple myeloma patients are linked to disease progression and could help guide immunotherapy.

## Contribution

The study identifies specific T cell subset dynamics and inhibitory receptor expression patterns in newly diagnosed multiple myeloma patients.

## Key findings

- NDMM patients have reduced T cell numbers and altered naïve and memory T cell balance.
- Activated follicular helper T cells correlate with increased bone marrow plasma cells in NDMM.
- Elevated inhibitory receptors on T cells suggest immune-driven disease progression in NDMM.

## Abstract

T cells are essential for tumor immunosurveillance and disease regulation in Multiple Myeloma (MM), but their role in disease pathogenesis is not well understood. To investigate this, we analyzed T cell subsets for activation status, relative distribution of naïve and memory T cell populations, regulatory T cells (Tregs), and circulating follicular helper T cells (cTFH) in the peripheral blood of 40 newly diagnosed MM (NDMM) patients. We also assessed inhibitory receptor expression CD160, ICOS/CD278, CD152/CTLA-4, and PD-1/CD279 on T cells in peripheral blood. Our results showed reduced T cell numbers, an imbalance between naïve and effector CD4+ T cells, and decreased memory Tregs in newly diagnosed MM patients compared to healthy controls. Furthermore, plasma cells in the bone marrow correlated with percentage of activated cTFH cells and inhibitory receptor expressing T cells in peripheral blood indicating that disrupted T cell homeostasis and immune-mediated processes may drive disease progression in NDMM.

•NDMM patients display decreased number of T-cells and altered balance of naïve and memory T cell subsets.•Disturbed equilibrium of naïve and memory Tregs is a key characteristic of NDMM patients.•Activated follicular helper T cells correlate with increased bone marrow plasma cells in NDMM.•Elevated levels of CD160, ICOS, CTLA-4, and PD-1 on T cells, along with their correlation to bone marrow plasma cells, indicate immune-driven disease progression in NDMM.•These T-cell abnormalities may be considered to harness the benefits of immunotherapy in NDMM.

NDMM patients display decreased number of T-cells and altered balance of naïve and memory T cell subsets.

Disturbed equilibrium of naïve and memory Tregs is a key characteristic of NDMM patients.

Activated follicular helper T cells correlate with increased bone marrow plasma cells in NDMM.

Elevated levels of CD160, ICOS, CTLA-4, and PD-1 on T cells, along with their correlation to bone marrow plasma cells, indicate immune-driven disease progression in NDMM.

These T-cell abnormalities may be considered to harness the benefits of immunotherapy in NDMM.