Spa­tial Repro­gram­ming of Immune Sur­veil­lance in Breast Can­cer: From Immune Con­trol to Immune Failure

Under­stand­ing how anti-tumour immu­ni­ty is organ­ised and dis­rupt­ed with­in the tumour microen­vi­ron­ment remains a cen­tral chal­lenge in breast can­cer. In this study, we inte­grate spa­tial­ly resolved imag­ing approach­es across matched tumour and lymph node sam­ples to define how immune sur­veil­lance is struc­tured and how it fails dur­ing dis­ease progression.

We iden­ti­fy dis­tinct spa­tial immune nich­es asso­ci­at­ed with effec­tive tumour con­trol, char­ac­terised by coör­di­nat­ed local­i­sa­tion of B cells. In con­trast, immune fail­ure is marked by dis­rupt­ed cel­lu­lar archi­tec­ture, altered immune cell traf­fick­ing, and the emer­gence of spa­tial­ly restrict­ed, dys­func­tion­al immune states. Notably, we observe a repro­gram­ming of B cell pop­u­la­tions and their inter­ac­tions with T cells, sug­gest­ing a crit­i­cal role for humoral – cel­lu­lar crosstalk in sus­tain­ing anti-tumour immunity.

By map­ping these tran­si­tions across tumour and drain­ing lymph node com­part­ments, we pro­pose a mod­el in which immune sur­veil­lance is gov­erned not only by cell com­po­si­tion but by spa­tial organ­i­sa­tion and inter­cel­lu­lar con­nec­tiv­i­ty. These find­ings pro­vide a frame­work for under­stand­ing resis­tance to treat­ments and high­light spa­tial­ly defined immune inter­ac­tions as poten­tial ther­a­peu­tic targets.