233 Myeloid-derived suppressor cells (MDSC) in psoriasis are an expanded population with diverse T cell-suppressor mechanisms

Abstract

Cutaneous metastases from breast cancer are common, occurring in 20-30% of patients with metastatic disease and is often the first site of disease recurrence. These metastases are often morbid, leading to significant pain, bleeding and psychological distress. Breast cancer is not considered a classically immunogenic tumor: incidence does not increase in immunosuppressed patients, spontaneous remission is very rare, and clinical trials of systemic immunotherapies such as anti-CTLA4 and anti-PD1 antibodies have shown poor or modest response rates. However, recent evidence suggests that pre-existing tumor infiltrating lymphocytes in breast cancer can predict overall survival and response to therapy. We hypothesized that skin directed therapies could increase the number of tumor infiltrating lymphocytes and ultimately lead to improved clinical response. Of 7 patients treated at our institution, average age was 55 (range 38 to 68 years old) and all had metastatic breast cancer with cutaneous involvement: 3 were ER/PR+, 2 were HER2+, and 2 were triple negative. Three patients received cryotherapy plus topical fluorouracil and 4 patients received a combination of cryotherapy, intra-lesional GM-CSF and imiquimod. Five of seven patients were treated with concurrent endocrine, targeted or chemotherapy. Biopsies available from 4 of the treated patients showed dramatic increases in the number of tumor infiltrating lymphocytes (up to 20 fold). Three patients had complete response in the skin including 2 of the patients (HER2+) demonstrated durable remission. An abscopal, or bystander effect, was noted in un-treated lesions, seen clinically and histologically as early as 2 weeks following treatment. We hypothesize that the skin directed therapies may create an in situ vaccination of the tumor thus enhancing tumor specific immune responses. Skin directed immunotherapies are easily administered, well tolerated and may improve clinical outcomes. 229Recipient skin resident memory T cells can induce GvHD-like dermatitis in human engrafted mice Graft-versus-Host-Disease (GvHD) is a major cause of illness and death in patients following hematopoietic stem cell transplantation (SCT). GvHD is assumed to result from donor-derived T cells attacking recipient tissues. However, GvHD is most common in the gut, liver and skin, tissues that contain large populations of long-lived resident memory T cells (T RM ). We have found that skin resident T cells survive classic conditioning regimens including total body irradiation and alemtuzumab. We hypothesize that surviving recipient-derived skin resident T cells may contribute to GvHD by interacting with newly generated donor-derived APC that have migrated into skin. To test this hypothesis, we grafted immunodeficient NSG mice with adult human skin containing T RM and then infused them 3 weeks later with equivalent numbers of either allogeneic PBMC (T cells + APC) or monocytes alone (APC). Skin grafts were harvested 3 weeks later and studied by histology, TCR sequencing and RT-PCR. In mice injecte...