PXD050766-1

PXD050766 is an original dataset announced via ProteomeXchange.

Title	Molecular signatures of T cells targeting multiple myeloma
Description	Wagner TR, Kehl N, Steiger S, Kilian M, Foster K, Boschert T, Hernandez GM, Abelin JG, Lindner K, Sester LS, Frenking JH, Schonfelder B, Schumacher S, Galas-Filipowicz D, Fitzsimons E, Green EW, Schmidt P, Uhrig S, Bunse L, Chain B, Muller-Tidow C, Goldschmidt H, Weinhold N, Frohling S, Muller-Tidow C, Carr SA, Yong K, Rippe K, Raab MS, Platten M, Eichmuller SB, and Friedrich MJ. 2024. T cell receptors (TCRs) play a crucial role in orchestrating cellular immunity in both health and disease and act as an essential component to detect infected or mutated cells. In cancer immunotherapy, microenvironmental cues and T cell repertoire composition are particularly important in mediating durable treatment responses. However, whether endogenous tumor reactive TCRs are commonly present in hematological cancers or mediate the effects of immunotherapy is currently unknown. Here, we employed a microfluidics-based forward screening approach of single T cells against autologous tumor cells to map T cell specificities and transcriptional phenotypes in bone marrow biopsies of treatment-naive patients with multiple myeloma. Together with MHC immunoprecipitation of autologous cancer cells, we established a comprehensive single-cell TCR atlas of the diseased human bone marrow, uncovering the cellular complexity and functional heterogeneity of naturally occurring tumor- and virus-specific TCRs. These analyses demonstrate clinically relevant endogenous anti-tumor reactivity in a rare subset of CD29 expressing bone marrow-resident T cells. In mouse tumor models, CD29 surface expression selectively indicated homing of tumor-specific, but not tumor-irrelevant TCRs. In patients with multiple myeloma, we found that tumor reactive T cells undergo selective clonal expansion in the bone marrow and in some cases recognize tumor antigens shared by multiple patients. Furthermore, the presence of tumor reactive T cells before treatment predicted clinical response to induction chemotherapy and bispecific antibody treatment in two patient cohorts. This antigen-agnostic dissection of the human bone marrow T cell repertoire enables the identification and monitoring of clinically relevant T cell responses targeting hematological cancers.
HostingRepository	MassIVE
AnnounceDate	2026-07-06
AnnouncementXML	Submission_2026-07-06_11:40:18.341.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karl Clauser
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	unknown modification; unknown modification; unknown modification; unknown modification; unknown modification
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-19 06:23:36	ID requested
⏵ 1	2026-07-06 11:40:18	announced

no publication

submitter keyword: immunopeptidomics, multiple myelom

Steven A. Carr
contact affiliation	Broad Institute of MIT and Harvard
contact email	scarr@broadinstitute.org
lab head
Karl Clauser
contact affiliation	Broad Institute of MIT and Harvard
contact email	clauser@broadinstitute.org
dataset submitter

MassIVE dataset URI

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