Interest in the lysosome’s potential role in anticancer therapies has recently been appreciated in the field of immuno-oncology. Targeting lysosomes triggers apoptotic pathways, inhibits cytoprotective autophagy, and activates a unique form of apoptosis known as immunogenic cell death (ICD). This mechanism stimulates a local and systemic immune response against dead-cell antigens. Stressors that can lead to ICD include an abundance of ROS which induce lysosome membrane permeability (LMP). Dying cells express markers that activate immune cells. Dendritic cells engulf the dying cell and then present the cell’s neoantigens to T cells. The discovery of ICD-inducing agents is important due to their potential to trigger autoimmunity. In this review, we discuss the various mechanisms of activating lysosome-induced cell death in cancer cells specifically and the strategies that current laboratories are using to selectively promote LMP in tumors.

Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence - a gap which can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells which can later present those tumorigenic antigens to T cells. We demonstrate that the oxidative agent native bovine xanthine oxidase can induce early markers of lysosome-induced immunogenic cell death in an in vitro human cancer cell line (CCL2). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of cells dosed with doxorubicin (a known inducer of LIICD). We looked at each marker at various time points after cancer cells were treated with xanthine oxidase, doxorubicin, and an untreated group. Upregulated biomarkers after treatment with the protein indicate an immunogenic response. Further, we used confocal imaging to show lysosomal membrane permeabilization after treatment with Native Bovine Xanthine Oxidase using Lucifer Yellow staining. We thus show the potential for this protein to induce an anticancer effect paired with an adaptive immune response against tumor cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method in patients and serve as the gateway to developing a new treatment approach against breast cancer. Citation Format: Iulianna Taritsa, Eric Fossel, Kuldeep Neote. Using lysosomal immunogenic cell death to target cancer via xanthine oxidase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4244.

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The flap success rate in the DIEP group was 100%. The alternative flap group had two partial flap failures, but none were total flap loss. The stacked flap group had only one total and one partial flap loss (success rate 97.7%). The overall complication rate was 19% in the DIEP group, 43% in the alternative flaps, and 13.6% for stacked flaps. The reconstruction flap method did have a significant difference in complication risk between the three groups (p-value 0.011). Compared to the DIEP flap group, alternative flaps (PAP or LAP) had a 3.107 higher risk of overall complication (p= 0.037). Stacked flaps, however, had a comparable risk for any complication to the DIEP flaps. There was no statistical difference in the number of secondary revisions needed or the total fat grafted between the three methods.Conclusions: Autologous breast reconstruction in low BMI patients yields successful and durable results in DIEP flap. This study shows that predictable results in the thin patient population can be obtained via alternate autologous methods beyond the gold standard DIEP flap.

Here we discuss the dramatic cutaneous reactions of two patients receiving targeted therapies for cancer (one on a MEK inhibitor/BRAF inhibitor and the other receiving carfilzomib). Demodicosis was the underlying cause in both cases, though the infection was mistaken for a reaction to the patients’ complex malignancy therapies. Given the prevalence of cutaneous side effects of chemotherapy and targeted cancer therapies and the protean nature of demodicosis, it follows that demodicosis may be easily mistaken as a drug reaction to a chemotherapeutic agent. Demodicosis in the setting of chemotherapy and immunosuppression must thus remain an important diagnostic consideration in patients undergoing cancer treatment to allow for appropriate diagnosis and management of cutaneous findings without discontinuation of essential chemotherapy.