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UNC Breast SPORE Research Project 2

Combining immune checkpoint inhibition with chemotherapy has transformed outcomes for patients with early stage triple negative breast cancer (TNBC).

However, treatment resistance and treatment-related toxicities persist as dual challenges that must be overcome with new strategies to guide personalized chemo-immunotherapy combinations.

We are investigating the role of DNA damage-induced necroptosis (inflammatory cell death) as a determinant of response to radiation therapy plus anti-PD1 (aPD1) immune checkpoint inhibitor combination therapy.

We use TNBC genetically engineered mouse models and correlative biomarker analyses of pre/post-treatment primary tumor, metastatic lymph node, and blood specimens from an ongoing clinical trial of preoperative aPD1 therapy, with or without radiation therapy, in early-stage TNBC with lymph node metastasis.

Caption available.
H&E stained primary tumor (left) and metastatic LN (right) at baseline and week 2.5 from a representative P-RAD patient treated with aPD1 alone (top row) or RT/aPD1 (24Gy, bottom row).

Project Aims

Aim 1

Assess necroptosis as a predictive biomarker of response to radiation therapy/aPD1 combination therapy in triple negative breast cancer.


Aim 2

Evaluate therapeutic neoantigen vaccination as a strategy to overcome ion therapy/aPD1 resistance induced by necroptosis deficiency.


Project Co-Leaders