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Poster Display session

258 - The effect of tumor derived HMBG1 on intra-tumoral B cells in esophageal squamous cell carcinoma

Date

14 Dec 2018

Session

Poster Display session

Presenters

Dora Kwong

Citation

Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493

Authors

D.L.W. Kwong1, Y.N. Kam2, X.Y. Guan2

Author affiliations

  • 1 Clinical Oncology, Queen Mary Hospital, NA - Hong Kong/HK
  • 2 Clinical Oncology, The University of Hong Kong, NA - Hong Kong/HK
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Resources

Abstract 258

Background

Tumor microenvironment (TME) is often hypoxic and characterized by diverse cell populations (tumor cells and lymphocytes). An intranuclear architectural protein termed high mobility group box chromosomal protein 1 (HMGB-1) is enriched in hypoxic environment, where it acts as a chemokine to promote recruitment of inflammatory cells. We studied the effect of tumor derived HMBG1 on B cell migration and phenotype differentiation in esophageal squamous cell carcinoma (ESCC).

Methods

Immunohistochemistry (IHC) staining for HMGB-1 was performed on tissue microarray (TMA) of ESCC and correlated with survival outcome. An immunostaining scoring system corresponding to total staining intensity as follows; (strong staining score =3; moderate staining score=2; weak staining scores= 1; no staining scores= 0). Co-staining with CD20+B was also performed to study B cells distribution in the tumor. ESCC cell lines were transfected with HMGB-1 and transwell migration of B cells were studied.

Results

TMA containing 78 paired primary tumors and normal tissue from ESCC patients was analyzed by IHC using an anti-HMGB1 antibody. We found that HMGB1 was expressed at a higher level as compared to paired normal tissue. Survival curves were estimated by the Kaplan-Meier method and compared with log-rank test to evaluate the relationship between biomarker HMGB1 and survival outcomes. Patients were divided into two groups based on the optimal cutoffs of low (score 0-1), high (score 2-3) staining of HMGB1, we found out that HMGB1 staining were not correlated to patient survivals (p = 0.363). We then performed double-staining and demonstrated that B cells were located in the stroma along HMGB1-stained tumor. Stable HMGB1 ESCC cell lines were established where boyden chamber and wound-healing assays demonstrated that B cells migrated and proliferated at higher rates towards HMGB1-overexpressing cell lines.

Conclusions

Our findings indicate that HMGB1 was over-expressed in tumor compared with normal tissue. HMGB1 expression per se was not correlated to survival in our log-rank analysis. HMGB1 expression has probable role in B cells recruitment, migration/proliferation.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Dora LW Kwong.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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