University of Wisconsin–Madison
Anna-Maria De Costa, Post Grad Trainee

Anna-Maria De Costa, MD, PhD

Radiation Oncology Resident

Department of Human Oncology

Education

General Surgery Preliminary Year, Medical University of South Carolina, (2014)

MD, PhD, Medical University of South Carolina, Medical Scientist Training Program (2014)

Selected Honors and Awards

ABS Best Fellowship Award (2016)

Intern of the Year, MUSC Department of Surgery (2015)

College of Graduate StudiesDistinguished Graduate of the Year (2014)

Ninth Annual Head and Neck Research Conference: First Place Oral Presentation (2011) (2011)

SCE&G Scholarship (2012–2013)

Eighth Annual Head and Neck Research Conference: First Place Oral Presentation (2010)

Student Research Day Poster Presentation: Second place for VAMC (2009)

Wachovia Hollings Cancer Center Scholarship (2008–2009)

Hollings Cancer Center Abney Scholarship (2007–2008)

University of Medical Associates Scholarship (06–07)

  • Modulation of therapeutic sensitivity by human papillomavirus. Radiother Oncol
    Swick AD, Chatterjee A, De Costa AM, Kimple RJ
    2015 Sep; 116 (3): 342-5
    • More

      Human papillomaviruses (HPVs) are small double-stranded DNA viruses that pose significant public health concerns as the causative agent of approximately 5% of worldwide cancers. The HPV oncogenes E6 and E7 play key roles in carcinogenesis. In the last 15years there has been a significant increase in the incidence of HPV-related head and neck cancers arising primarily in the oropharynx. Patients with HPV-positive head and neck cancers (HNCs) have a significantly improved prognosis compared to those with HPV-negative disease. In this review we will discuss data suggesting how HPV oncogenes modulate both the intrinsic radiation sensitivity of HNCs and also have important effects upon the tumor microenvironment. Together, these findings contribute to the improved outcomes seen in patients with HPV-positive HNC.

      View details for PubMedID 26364887
  • Incorporating Patient Satisfaction Metrics in Assessing Multidisciplinary Breast Cancer Care Quality. South Med J
    Harper JL, De Costa AM, Garrett-Mayer E, Sterba KR
    2015 Jun; 108 (6): 372-6
    • More

      OBJECTIVES: The Medical University of South Carolina implemented a patient-centered multidisciplinary breast clinic program (MDBC) in August 2012. In this study, patient satisfaction with the MDBC care delivery model and communication with healthcare providers was examined to inform the refinement of the MDBC program.

      METHODS: During the first 10 months of the MDBC, patients were asked to complete a 14-question postconsultation telephone survey. A statistical analysis was performed to explore potential associations between age, race, and stage with overall patient satisfaction scores.

      RESULTS: Overall, patients (N = 52, 56% white, 42% African American, 2% Hispanic; mean age 61 years) rated the quality of care highly (mean 4.7, range [1 = poor to 5 = excellent]) and felt comfortable with their plan of care (mean 1.63, range [1 = extremely comfortable to 5 = not at all comfortable]). No statistically significant differences in overall satisfaction were found by age, race, or stage; however, patient responses were commonly not optimal (ie, either "no" or "yes, but not as much as I would like") when asked if the care team addressed the impact of their diagnosis on personal relationships (40.4%) or emotional health (28.9%).

      CONCLUSIONS: Patients were highly satisfied with the care they received in the MDBC program. Findings suggest that this model is well suited to a diverse patient population and have highlighted quality improvement targets such as increased emphasis on providers' communication about psychosocial issues.

      View details for PubMedID 26079465
  • An Inflammatory Cytokine Milieu is Prominent in Premalignant Oral Lesions, but Subsides when Lesions Progress to Squamous Cell Carcinoma. J Clin Cell Immunol
    Woodford D, Johnson SD, De Costa AM, Young MR
    2014 Jun; 5 (3):
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      While head and neck squamous cell carcinomas (HNSCC) are associated with profound immune suppression, less is known about the immunological milieu of premalignant oral lesions. The present study shows dynamic shifts in the immune milieu within premalignant oral lesions and when they have progressed to HNSCC. Specifically, this study showed that the premalignant lesion environment consists of inflammatory mediators and IL-17, but this inflammatory phenotype declines when premalignant oral lesions have progressed to HNSCC. The cytokine profiles of human tissues did not correspond with plasma cytokine profiles. A murine carcinogen-induced premalignant lesion model that progresses to HNSCC was used to examine cytokine profiles released from tissues as well as regional lymph nodes. As in human tissues, murine premalignant lesions and regional lymph nodes released high levels of inflammatory cytokines and, very prominently, IL-17. Also similar to human tissues, release of inflammatory cytokines declined in HNSCC tissues of mice and in the regional lymph nodes of mice with HNSCC. Studies focusing on IL-17 showed that mediators from premalignant lesions stimulated normal spleen cells to produce increased levels of IL-17, while mediators from HNSCC were less stimulatory toward IL-17 production. IL-17 production by Th17-skewed CD4+ cells was strongly inhibited by normal oral epithelium as well as HNSCC. In contrast, premalignant lesion-derived mediators further increased IL-17 production by Th17-skewed cells. The stimulation of IL-17 production by premalignant lesions was dependent on IL-23, which premalignant lesions released in higher amounts than control tissues or HNSCC. HNSCC tissues instead produced increased levels of TGF-β compared to premalignant lesions, and skewed normal spleen cells toward the Treg phenotype. This skewing was blocked by supplementation with IL-23. These studies suggest IL-23 to be a significant contributor to the inflammatory IL-17 phenotype in premalignant oral lesions and suggest the decline in IL-23 in HNSCC leads to a decline in Th17 cells.

      View details for PubMedID 25419481
  • Effect of the premalignant and tumor microenvironment on immune cell cytokine production in head and neck cancer. Cancers (Basel)
    Johnson SD, De Costa AM, Young MR
    2014 Apr 02; 6 (2): 756-70
    • More

      Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE2 compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC.

      View details for PubMedID 24698959
  • Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response. Int Immunopharmacol
    De Costa AM, Justis DN, Schuyler CA, Young MR
    2012 Jul; 13 (3): 322-30
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      The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions that progress to HNSCC. As previous studies demonstrated that premalignant lesions and HNSCC overexpress common tumor antigens, bone marrow-derived DCs were pulsed with premalignant lesion lysate (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions. Lesion progression was tracked through endoscopy, which revealed that DCpm vaccination and control vaccination with dendritic cells pulsed with normal tongue epithelium lysate (DCnt) significantly decreased lesion burden at 8weeks. Analysis of lymph node cells revealed that while DCnt vaccination resulted in a rapid increase in total lymphocyte count, levels of activated conventional CD4(+) T cells and Th1, Tc1, Th17, Tc17, and Th2 cells, DCpm vaccination results in a delayed, yet substantial, increase in these immune effector mechanisms. This suggests that dendritic cell vaccination may have a beneficial effect on clinical outcome regardless of type of antigenic stimulation. Also, pulsing DCs with premalignant lysate rather than normal tongue epithelium lysate affects the dendritic cells in a way that delays the immune effector response upon vaccination of premalignant lesion-bearing mice.

      View details for PubMedID 22609090
  • Immunological modulation by 1α,25-dihydroxyvitamin D3 in patients with squamous cell carcinoma of the head and neck. Cytokine
    Walker DD, Reeves TD, de Costa AM, Schuyler C, Young MR
    2012 Jun; 58 (3): 448-54
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      Prior studies showing that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] stimulated intratumoral immune infiltration were extended to analysis of cytokine profiles in the periphery and in oral tissues. Most prominent was the disparity between cytokine levels in plasma and in either pathologically normal oral tissue or HNSCC tissue from patients that were untreated or treated with 1,25(OH)(2)D(3). Levels of IL-6 and IL-10, but not IL-2, IFN-γ or TNF-α, tended to be increased in the plasma of HNSCC patients and 1,25(OH)(2)D(3) further increased plasma levels of all of these cytokines. While these cytokines tended to be increased in HNSCC tissue, 1,25(OH)(2)D(3) resulted in variable cytokine responses that showed a general tendency toward further increased levels. Levels of IL-8 and VEGF were increased in plasma and tissue of untreated HNSCC patients, and were further increased in plasma, but not in tissues, of patients treated with 1,25(OH)(2)D(3). Levels of IL-1α and IL-1β were similar in plasma of controls and HNSCC patients, but were increased in HNSCC tissues. In contrast to that seen in plasma where 1,25(OH)(2)D(3) increased levels of IL-1α and IL-1β, this was not seen in tissue following 1,25(OH)(2)D(3) treatment. These results show a discordant relationship between systemic and intratumoral cytokine profiles and suggest a tendency of 1,25(OH)(2)D(3)to increase a multitude of cytokines within tumor tissue.

      View details for PubMedID 22450225
  • Characterization of the evolution of immune phenotype during the development and progression of squamous cell carcinoma of the head and neck. Cancer Immunol Immunother
    De Costa AM, Schuyler CA, Walker DD, Young MR
    2012 Jun; 61 (6): 927-39
    • More

      While studies have indicated that squamous cell carcinoma of the head and neck (HNSCC) is associated with immune suppression, these studies did not analyze the immune response at the dysplastic stage. The present study utilized a mouse model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis to examine the alterations in immune phenotype at the premalignant and malignant stages of HNSCC. Cervical lymph nodes of HNSCC-bearing mice were found to contain a greater number of cells, including a greater number of conventional (Tconv) and regulatory (Treg) T cells, compared to cervical lymph nodes of control and premalignant lesion-bearing mice, though the Tconv cells appear to be less proliferative and the Treg cells appear to be less suppressive at the HNSCC stage. Premalignant lesion-bearing mouse lymph nodes consist of a greater percentage of Tconv cells expressing markers for activation, memory, and exhaustion compared to both control and HNSCC-bearing mice. Also, lymph nodes' cells from both premalignant lesion-bearing and HNSCC-bearing mice include increased levels of Th1, Tc1, and Th17 cells, with no differences in levels of Th2 cells, compared to control mice. The data show that while there is the expected increase in immunosuppressive Tregs in lymph nodes when HNSCC is present, there is also an unexpected increase in immune populations usually associated with a beneficial antitumor response, including Tconv cells and Th1 and Tc1 cells. In addition, the results demonstrate that the premalignant stage of HNSCC development is associated with a robust immune response involving an increase in inflammatory Th1, Tc1, and Th17 cells.

      View details for PubMedID 22116344
  • Defining a role for sphingosine kinase 1 in p53-dependent tumors. Oncogene
    Heffernan-Stroud LA, Helke KL, Jenkins RW, De Costa AM, Hannun YA, Obeid LM
    2012 Mar 01; 31 (9): 1166-75
    • More

      p53 is a crucial tumor suppressor that is mutated or deleted in a majority of cancers. Exactly how p53 prevents tumor progression has proved elusive for many years; however, this information is crucial to define targets for chemotherapeutic development that can effectively restore p53 function. Bioactive sphingolipids have recently emerged as important regulators of proliferative, apoptotic and senescent cellular processes. In this study, we demonstrate that the enzyme sphingosine kinase 1 (SK1), a critical enzyme in the regulation of the key bioactive sphingolipids ceramide, sphingosine and sphingosine-1-phosphate (S1P), serves as a key downstream target for p53 action. Our results show that SK1 is proteolysed in response to genotoxic stress in a p53-dependent manner. p53 null mice display elevation of SK1 levels and a tumor-promoting dysregulation of bioactive sphingolipids in which the anti-growth sphingolipid ceramide is decreased and the pro-growth sphingolipid S1P is increased. Importantly, deletion of SK1 in p53 null mice completely abrogated thymic lymphomas in these mice and prolonged their life span by ~30%. Deletion of SK1 also significantly attenuated the formation of other cancers in p53 heterozygote mice. The mechanism of p53 tumor suppression by loss of SK1 is mediated by elevations of sphingosine and ceramide, which in turn were accompanied by increased expression of cell cycle inhibitors and tumor cell senescence. Thus, targeting SK1 may restore sphingolipid homeostasis in p53-dependent tumors and provide insights into novel therapeutic approaches to cancer.

      View details for PubMedID 21765468
  • Immunotherapy for head and neck cancer: advances and deficiencies. Anticancer Drugs
    De Costa AM, Young MR
    2011 Aug; 22 (7): 674-81
    • More

      The concept of immunotherapy as a treatment for cancer patients has been in existence for decades. However, more recent immune therapeutic approaches have involved targeting of tumor-specific antigens. Although improvements have been made in using such immune stimulatory treatment strategies for a variety of solid cancers, the use of these strategies for patients with head and neck squamous cell carcinoma (HNSCC) is lagging behind. Immunotherapeutic approaches for HNSCC are particularly complicated by the profound immune suppression that is induced by HNSCC, which potentially decreases the effectiveness of immune stimulatory efforts. Trials involving patients with various solid cancers have shown the enhanced effectiveness of combining various immunotherapeutic approaches or combining immunotherapy with chemotherapy or radiation therapy. Treatment of HNSCC with such combination approaches has not been extensively investigated and has the added challenge of the need to overcome the HNSCC-induced immune suppression. This study focuses on clinical trials that have tested immunotherapeutic approaches for HNSCC patients and the challenges associated with such approaches. In addition, it will call attention to immunotherapeutic strategies that have been shown to be successful in the treatment of other solid cancers to identify potential strategies that may apply to the treatment of HNSCC.

      View details for PubMedID 21037467
  • Use of alpha,25-dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma. Hum Immunol
    Walsh JE, Clark AM, Day TA, Gillespie MB, Young MR
    2010 Jul; 71 (7): 659-65
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      Prior studies have shown that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduced intratumoral levels of immune inhibitory CD34(+) progenitor cells while increasing levels of mature progeny dendritic cells. This finding was extended to a pilot study to determine whether 1,25(OH)(2)D(3) treatment concurrently increases levels of intratumoral CD4(+) and CD8(+) T cells, increases intratumoral levels of immune cells expressing the early activation marker CD69, and prolongs time to HNSCC recurrence. The clinical trial comprised 16 patients with newly diagnosed HNSCC being untreated and 16 patients being treated with 1,25(OH)(2)D(3) during the 3-week interval between cancer diagnosis and surgical treatment. Immunologic effects of treatment were monitored by immunohistochemical analyses of surgically removed HNSCC. Clinical effectiveness of 1,25(OH)(2)D(3) treatment in this study was measured by the time to HNSCC recurrence. HNSCC tissues of patients who received treatment with 1,25(OH)(2)D(3) contained increased levels of CD4(+) cells and, more significantly, CD8(+) T cells. Also prominent was an increase in cells expressing the lymphoid activation marker CD69. Results of this pilot study suggest that patients treated with 1,25(OH)(2)D(3) had a lengthier time to tumor recurrence compared with patients who were not treated before surgery.

      View details for PubMedID 20438786
  • NK depletion results in increased CCL22 secretion and Treg levels in Lewis lung carcinoma via the accumulation of CCL22-secreting CD11b+CD11c+ cells. Int J Cancer
    Mailloux AW, Clark AM, Young MR
    2010 Dec 01; 127 (11): 2598-611
    • More

      Tumor-induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T-cells (Tregs). Previous studies demonstrated that NK-dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK-derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC-bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK-depleted LLC-bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22-producing cellular fractions in LLC-bearing lungs. A novel CD11b(+)CD11c(+) cell population was identified that accumulates in large numbers in NK-depleted LLC-bearing lung tissue. These CD11b(+)CD11c(+) cells secreted large amounts of CCL22 that may overcompensate for the loss of NK-derived CCL22 in the lungs of NK-depleted LLC-bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC-bearing lungs.

      View details for PubMedID 20198623

 

 

Contact Information

Anna-Maria De Costa, MD, PhD

600 Highland Avenue,
Madison, WI 53792
Email