Abstract B005: Intralesional injections with checkpoint inhibitors and cytokines can modify DCIS lesions with infiltrating T cells
Authors: Schindler Nicole F. , Glencer Alexa , Miller Phoebe , Schwartz Christopher , Hirst Gillian , Borowsky Alexander , Campbell Michael , Esserman Laura 
Published: December 2022

Abstract
Background: Ductal carcinoma in situ (DCIS) is a risk factor for the development of invasive ductal carcinoma. Previous work has shown that an increased presence of T cells corresponds to high-risk DCIS features: age &lt;45 years, size &gt;5 cm, high-grade, palpable mass, hormone receptor negativity, and HER2 positivity. The presence of T cells colocalized with tumor is emerging as a predictor of response to checkpoint inhibition in invasive cancer. We previously have demonstrated that intratumoral injections of a checkpoint inhibitor (pembrolizumab) in DCIS resulted in an increased number of T cells, but without tumor cell killing. We hypothesized that the addition of an agent that could potentiate both innate and adaptive immune responses might increase the efficacy of checkpoint inhibition. Methods/Materials: We administered intralesional injections of immunotherapy (4-8 mg pembrolizumab + 2-4mg mRNA 2752) to patients with “high-risk” DCIS in an attempt to modulate the immune system and protect from disease progression and recurrence. Two patients have been enrolled and completed therapy and 4 more are being treated. Immune infiltrates were characterized by multiplex immunofluorescence (mIF) staining of pre- and post-treatment tissue samples using two 6-plex panels. Staining was performed on a Leica Bond autostainer and images were acquired on a Vectra Polaris imaging system. Image analysis was performed utilizing inForm and QuPath software packages, as well as R scripts. Results: The first patient treated, a 41-year-old woman with ER+/PR+, HER2- disease, with low T cells in her pre-treatment biopsy, received one dose of pembrolizumab (8mg) with mRNA 2752 (4mg). While she experienced fatigue, sustained fever, and muscle aches for 3-5 days, draining node enlargement and redness and swelling at the breast a week after treatment, there was no change on her post-treatment MRI, and no significant change in the number of T cells in her post-treatment tissue. The second patient, a 74-year-old woman with ER-/PR-, HER2+ disease had high numbers of T cells in the pre-treatment biopsy. She received one injection of pembrolizumab (4mg) with mRNA 2752 (2mg), followed 3 weeks later by an injection of pembrolizumab (4mg) alone. She declined the second dose of mRNA 2752 due to side effects from the first injection. Her post-treatment MRI showed some reduction in tumor volume and her post-treatment biopsy showed no evidence of DCIS, as well as an increase in T cells. Conclusions: The presence of T cells prior to therapy is likely to be important for eliciting a strong anti-tumor response. The addition of an agent that enhances both innate and adaptive immune responses may increase the efficacy of immune checkpoint blockade. Four additional patients will have completed their therapy by the end of August and we await results. It will be important to understand if pre-existing T cells within the DCIS lesion are a predictor for response to therapy as we continue to screen and enroll patients.
Citation Format: Nicole F. Schindler, Alexa Glencer, Phoebe Miller, Christopher Schwartz, Gillian Hirst, Alexander Borowsky, Michael Campbell, Laura Esserman. Intralesional injections with checkpoint inhibitors and cytokines can modify DCIS lesions with infiltrating T cells [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B005.