Pathogenesis of BIA-ALCL Print

The ASERF Scientific Research Committee and Board of Directors are pleased to announce the following grant award:

Researcher: Marshall Kadin, MD

Grant Award: ASERF Interim Grant

Amount Awarded: $ 193,110

Project Name: Pathogenesis  of BIA-ALCL

Project Summary: Hypothesis: Anaplastic cells in BIA-ALCL produce cytokines that shape the tumor microenvironment (Figure 1). Our preliminary results indicate that anaplastic cells in culture produce IL-13 which induces immunoglobulin heavy chain class switch of plasma cells to produce IgE. We found IgE bound to the surface of mast cells and antigen presenting cells (APC) within involved tissues. Mast cells produce prostaglandin D2 (PGD2) which recruits Th2 cells and eosinophils prominent in BIA-ALCL lesions. A possible source of IgE is plasma cells in tumors and regional lymph nodes. Neither IL-13, IgE nor PGD2 has been quantified in malignant seromas before nor after treatment or compared to benign seromas. Whether IgE binds to bacteria or tumor associated antigens also has not been explored. IL-13 can be produced by effector T cells and innate lymphoid cells (ILCs) which will be addressed in this proposal. We hypothesize there will be different clinical presentations according to the cellular origin and functional polarization of anaplastic cells, specifically the Th1/ILC1 phenotype may associated with clinically indolent behavior and the Th3/ILC3 phenotype with invasive tumors.

To address our hypothesis our specific aims are:

Aim 1- Determine the significance of cytokine, prostaglandin D2 and IgE levels in benign and malignant seroma fluids and blood at clinical presentation and after treatment.

Aim 2- Determine if anaplastic cells are derived from effector T cells or innate lymphoid cells.

   Subaim 1- Determine which subset anaplastic cells belong to- Th1/1LC1, Th2/ILC2, or Th3/ILC3.

   Subaim 2- Is there a difference in subsets between in situ and invasive disease?

   Subaim 3- Can Th3/ILC3 anaplastic cells be repolarized to Th1/ILC1?

Aim 3- Identify precursors of BIA-ALCL with a similar phenotype in capsules, seroma fluids and regional lymph nodes.

AIM 4- Determine if IgE binds to bacterial and/or tumor associated antigens