Researchers have identified a subset of marrow infiltrating lymphocytes (MILs) that appear to display a stemlike/resident phenotype. According to data presented at the 2019 Society for Immunotherapy of Cancer (SITC) meeting, additional studies could “determine whether this population can be exploited and/or enriched to improve the efficacy of adoptive T cell therapy” in multiple myeloma.1

Previous studies have shown that MILs have increased antitumor reactivity and proliferative capacity compared with peripheral blood lymphocytes. However, “despite the recent identification of a core signature for tissue resident memory T cells, a definitive bone marrow-resident T-cell phenotype has yet to be identified.”

To attempt to do that, researchers used multiparametric flow cytometry to perform single-cell analysis on CD8+ T cells taken from patients with myeloma to identify subsets of cells that are enriched in the bone marrow compared with peripheral blood.

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The activation and tissue retention marker CD69 identified a population of CD8+ MILs that were all but absent in the peripheral blood, according to the researchers. This population of MILs also displayed peculiar phenotypic and functional features compared with CD69-negative counterparts.

In addition, this population of MILs displayed increased levels of CXCR6 and variable levels of CD101, despite a virtual absence of CD103 expression. “Interestingly, CD101 had been associated with both tissue residency and exhaustion,” the researchers wrote in their abstract. “As such, its variable expression may depend on multiple myeloma burden.”

In addition, these MILs had a unique phenotype that is linked with preserved cytotoxic activity and proliferative capacity. Specifically, they displayed intermediate expression of exhaustion markers such as TIGIT, TIM3, and PD1, increased CD27, and markedly reduced CD57.

On the whole, the researchers wrote, CD69+ MILS were clearly distinct from their counterparts in the peripheral blood and from CD69- counterparts. They displayed higher levels of TCF1, CD27, CXCR6, and high CXCR4 levels, with reduced expression of both CD57 and T-bet.

Reference

Biavati L, Heimann M, Zawidzka E, et al. Bone marrow infiltrating lymphocytes possess a resident memory, stem-like phenotype that may account for enhanced antitumor efficacy in multiple myeloma-implications for adoptive T cell therapy. Presented at the 2019 Society for Immunotherapy of Cancer (SITC) meeting; November 6-10, 2019: National Harbor, MD. Abstract P551.