MADHAV DHODAPKAR (ATLANTA)
UNDERSTANDING IMMUNE ME OF SMM
Emory University, Atlanta, GA, USA
It is now well appreciated that all cases of myeloma are preceded by a precursor phase. Prior
studies have shown that the immune system has the capacity to specifically recognize these
lesions(1). In a prospective study, the presence of T cell response correlated with the risk of
progression to clinical MM(2). The potential importance of host response in controlling the
growth of human MM is also illustrated in humanized models, wherein the tumor cells mediate
progressive growth in vivo(3). In recent studies utilizing single cell approaches, we and others
have shown that there are several changes in the immune microenvironment that begin before
the evolution of clinical myeloma(4, 5). Progression to clinical myeloma is accompanied by
attrition of T cells with stem-like memory phenotype, as well as changes in innate and myeloid
cells. We suggest that as with genomics of tumor cells, tumor microenvironment in each patient
is distinct in terms of cellular composition and cell states. Our current hypothesis is that the
immune microenvironment co-evolves with changes in tumor cells, with changes in both
compartments impacting the other. This cross-talk has direct implications for harnessing
immune based approaches to prevent clinical MM.
References:
1. M. V. Dhodapkar, J. Krasovsky, K. Osman, M. D. Geller, Vigorous premalignancy-specific
effector T cell response in the bone marrow of patients with monoclonal gammopathy. J Exp
Med 198, 1753-1757 (2003).
2. M. V. Dhodapkar et al., Prospective analysis of antigen-specific immunity, stem-cell antigens,
and immune checkpoints in monoclonal gammopathy. Blood 126, 2475-2478 (2015).
3. R. Das et al., Microenvironment-dependent growth of preneoplastic and malignant plasma
cells in humanized mice. Nat Med 22, 1351-1357 (2016).
4. J. K. Bailur et al., Early alterations in stem-like/resident T cells, innate and myeloid cells in the
bone marrow in preneoplastic gammopathy. JCI Insight 5, (2019).
5. O. Zavidij et al., Single-cell RNA sequencing reveals compromised immune microenvironment
in precursor stages of multiple myeloma. Nature Cancer 1, 493-506 (2020).