Advanc­ing BIA-ALCL Research Through a UK – PORT Alliance — From Biobank­ing to Immune Discovery

Breast implant-asso­ci­at­ed anaplas­tic large cell lym­phoma (BIA-ALCL) is a rare T‑cell lym­phoma aris­ing in the con­text of chron­ic inflam­ma­tion, yet its sys­temic immune land­scape remains poor­ly defined. This study aimed to char­ac­terise immune alter­ations in BIA-ALCL patients (n=22) com­pared with con­trol cohorts, includ­ing implant-pos­i­tive (BIA-ALCL – neg­a­tive; n=15) and implant-neg­a­tive (n=22) individuals. 

High-dimen­sion­al immune pro­fil­ing and Olink-based pro­teom­ic analy­sis were per­formed to quan­ti­fy cir­cu­lat­ing immune cell sub­sets and serum bio­mark­ers across dis­ease and health. Com­par­a­tive analy­ses were con­duct­ed between BIA-ALCL, healthy donors, and con­trol groups. In addi­tion, in vit­ro assays were per­formed to assess the effects of smooth and tex­tured implant shells on the immune reper­toire of periph­er­al blood from implant-neg­a­tive healthy donors. 

High-dimen­sion­al flow cytom­e­try reveals a diver­gent immune sig­na­ture in BIA-ALCL dif­fer­en­ti­at­ing from the con­trol cohorts where a proin­flam­ma­to­ry shift was observed. BIA-ALCL is char­ac­terised by a pro-inflam­ma­to­ry, mem­o­ry-skewed immune phe­no­type, with reduced Th2 and increased Th1/Th17.1 polar­i­sa­tion in CD4 T cells, along­side loss of naïve and expan­sion of mem­o­ry sub­sets across T and NK cells. Immune acti­va­tion is dys­reg­u­lat­ed across CD4, CD8, γδ T cells and NK cells, with reduced CD25/CD69, vari­able CD30 expres­sion, and con­text-depen­dent exhaus­tion, par­tic­u­lar­ly enriched in Vδ1 γδ T cells. 

Addi­tion­al­ly, BIA-ALCL is char­ac­terised by impaired anti­gen pre­sen­ta­tion and innate remod­el­ling, with altered B‑cell mat­u­ra­tion, reduced pDCs, and dys­func­tion­al mono­cyte com­part­ments. Col­lec­tive­ly, these find­ings define an immuno­log­i­cal­ly dys­reg­u­lat­ed sys­temic envi­ron­ment in BIA-ALCL, pro­vid­ing insight into the dis­ease biology.