Abstract
Dysproteinemias progress through a series of clonal evolution events in the tumor cell along with the development of a progressively more “permissive” immune tumor microenvironment (iTME). Novel multiparametric cytometry approaches, such as cytometry by time-of-flight (CyTOF) combined with novel gating algorithms can rapidly characterize previously unknown phenotypes in the iTME of tumors and better capture its heterogeneity. Here, we used a 33-marker CyTOF panel to characterize the iTME of dysproteinemia patients (MGUS, multiple myeloma—MM, smoldering MM, and AL amyloidosis) at diagnosis and after standard of care first line therapies (triplet induction chemotherapy and autologous stem cell transplant—ASCT). We identify novel subsets, some of which are unique to the iTME and absent from matched peripheral blood samples, with potential roles in tumor immunosurveillance as well as tumor immune escape. We find that AL amyloidosis has a distinct iTME compared to other dysproteinemias with higher myeloid and “innate-like” T cell subset infiltration. We show that T cell immune senescence might be implicated in disease pathogenesis in patients with trisomies. Finally, we demonstrate that the early post-ASCT period is associated with an increase of senescent and exhausted subsets, which might have implications for the rational selection of post-ASCT therapies.
| Original language | English (US) |
|---|---|
| Article number | 72 |
| Journal | Blood cancer journal |
| Volume | 9 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2019 |
Fingerprint
ASJC Scopus subject areas
- Hematology
- Oncology
Cite this
Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies. / Kourelis, Taxiarchis; Villasboas Bisneto, Jose (J.C.); Jessen, Erik; Dasari, Surendra; Dispenzieri, Angela; Jevremovic, Dragan; Kumar, Shaji K.
In: Blood cancer journal, Vol. 9, No. 9, 72, 01.09.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies
AU - Kourelis, Taxiarchis
AU - Villasboas Bisneto, Jose (J.C.)
AU - Jessen, Erik
AU - Dasari, Surendra
AU - Dispenzieri, Angela
AU - Jevremovic, Dragan
AU - Kumar, Shaji K
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Dysproteinemias progress through a series of clonal evolution events in the tumor cell along with the development of a progressively more “permissive” immune tumor microenvironment (iTME). Novel multiparametric cytometry approaches, such as cytometry by time-of-flight (CyTOF) combined with novel gating algorithms can rapidly characterize previously unknown phenotypes in the iTME of tumors and better capture its heterogeneity. Here, we used a 33-marker CyTOF panel to characterize the iTME of dysproteinemia patients (MGUS, multiple myeloma—MM, smoldering MM, and AL amyloidosis) at diagnosis and after standard of care first line therapies (triplet induction chemotherapy and autologous stem cell transplant—ASCT). We identify novel subsets, some of which are unique to the iTME and absent from matched peripheral blood samples, with potential roles in tumor immunosurveillance as well as tumor immune escape. We find that AL amyloidosis has a distinct iTME compared to other dysproteinemias with higher myeloid and “innate-like” T cell subset infiltration. We show that T cell immune senescence might be implicated in disease pathogenesis in patients with trisomies. Finally, we demonstrate that the early post-ASCT period is associated with an increase of senescent and exhausted subsets, which might have implications for the rational selection of post-ASCT therapies.
AB - Dysproteinemias progress through a series of clonal evolution events in the tumor cell along with the development of a progressively more “permissive” immune tumor microenvironment (iTME). Novel multiparametric cytometry approaches, such as cytometry by time-of-flight (CyTOF) combined with novel gating algorithms can rapidly characterize previously unknown phenotypes in the iTME of tumors and better capture its heterogeneity. Here, we used a 33-marker CyTOF panel to characterize the iTME of dysproteinemia patients (MGUS, multiple myeloma—MM, smoldering MM, and AL amyloidosis) at diagnosis and after standard of care first line therapies (triplet induction chemotherapy and autologous stem cell transplant—ASCT). We identify novel subsets, some of which are unique to the iTME and absent from matched peripheral blood samples, with potential roles in tumor immunosurveillance as well as tumor immune escape. We find that AL amyloidosis has a distinct iTME compared to other dysproteinemias with higher myeloid and “innate-like” T cell subset infiltration. We show that T cell immune senescence might be implicated in disease pathogenesis in patients with trisomies. Finally, we demonstrate that the early post-ASCT period is associated with an increase of senescent and exhausted subsets, which might have implications for the rational selection of post-ASCT therapies.
UR - http://www.scopus.com/inward/record.url?scp=85071637133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071637133&partnerID=8YFLogxK
U2 - 10.1038/s41408-019-0234-4
DO - 10.1038/s41408-019-0234-4
M3 - Article
C2 - 31462637
AN - SCOPUS:85071637133
VL - 9
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 9
M1 - 72
ER -