Camilla Engblom Team

Targeting the immune system to treat tumors has revolutionized cancer care, but many patients fail to respond to current immunotherapies. Thus, there is an urgent need to expand treatment options. In the lab, we study B cells and B cell-derived antibody-producing plasma cells that have recently emerged as promising, yet untapped, therapeutic targets in cancer. B lineage cells are compelling to study because they: i) infiltrate tumors and associate with positive prognosis and immunotherapy outcome across cancers, ii) present antigen to T cells, and iii) express clonal heritable B cell receptors (BCR) that confer exquisite molecular (i.e., antigen) specificity. B cell receptors can be defined by sequencing, but these methods require tissue dissociation, which loses the anatomical location, and the surrounding functionally relevant environmental cues. Linking specific BCR sequences to their molecular and cellular surroundings, i.e., ‘clonal niche’, could help us understand and harness B and plasma cell anti-tumor activity, e.g., by boosting endogenous responses and/or producing tumor-targeting antibodies. A current technological bottleneck has been to capture the location of BCR sequences, and by extension B and plasma cell clonal responses, directly within tissues. In the lab, we use cutting-edge, in-house developed, spatial transcriptomics (ST)-based technology (Spatial VDJ) to systematically interrogate B and plasma cell clonal biology in cancer and beyond.

We have several on-going research projects in the lab, including to:

• Discover and functionally interrogate B and plasma cell clonal repertoire and niches during tumor progression and immunotherapy using mouse models
• Uncover B and plasma cell spatial clonal evolution and reactivities in human tumors
• Further develop Spatial VDJ and related technologies

Combined, we aim to understand aspects of where, when, and how B and plasma cell clones evolve and their functions with a focus on cancer. Our investigations into patient tumors and unique sample pipeline could help identify key tumor-regulatory BCR sequences and putative biomarkers. Long-term, our research program aims to find new ‘druggable’ antibody-based therapies against cancers and help develop the use of engineered ‘CAR-B’ cells or plasma cell-producing anti-tumor antibodies in situ.

Camilla Engblom, assistant professor, camilla.engblom@ki.se

Yang Zhao, PhD student, yang.zhao.4@ki.se
María José Pino, research assistant, maria.jose.pino.vasquez@ki.se
Yuqing Zhou, research assistant, yuqing.zhou@ki.se
Xenia Tolstoy, research assistant/lab manager
Tilak Das, research assistant, tilak.das@ki.se
Samayeen Rahman, bachelor student, qazi.samayeen.rahman@ki.se
Joseba Gollastegui Goni, bachelor student, joseba.gallastegui.goni@stud.ki.se

Affiliated: Mariia Guryleva, PhD student