Nicolas Llosa, MD

Director, Pediatric Sarcoma Program

As an Associate Professor of Pediatrics and Oncology, Dr. Llosa’s research focuses on developing and advancing immunotherapy approaches for sarcomas, with an emphasis on understanding how the immune system interacts with these tumors and how those interactions can be therapeutically exploited.

Sarcomas are a diverse group of cancers that arise in bone and soft tissues, including muscle, fat, blood vessels, nerves, and other connective tissues. They can occur at any age, although several sarcoma subtypes, including rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma, disproportionately affect children, adolescents, and young adults. Because sarcomas encompass many biologically distinct diseases, treatment depends on the specific tumor type, location, stage, molecular characteristics, and other clinical factors. Despite important advances in surgery, radiation therapy, and chemotherapy, outcomes remain poor for many patients with recurrent, metastatic, or treatment-resistant disease, highlighting the need for new therapeutic strategies.

Dr. Llosa’s laboratory investigates the sarcoma tumor immune microenvironment to better understand why some tumors are recognized and attacked by the immune system while others remain immunologically resistant. A major goal of this work is to identify mechanisms that suppress effective antitumor immunity and to develop strategies that can restore or enhance immune responses against sarcoma cells.

A central area of interest is cancer immunotherapy, a group of treatments designed to harness or strengthen the body's natural immune defenses against cancer. Immunotherapeutic approaches can work by enhancing the ability of immune cells to recognize tumor cells, reversing mechanisms of immune suppression, stimulating antitumor immune responses, or directly targeting molecules expressed by cancer cells or cells within the tumor microenvironment. These strategies include immune checkpoint inhibitors, monoclonal antibodies, cellular therapies, cancer vaccines, and other immune-modulating agents.

Particular emphasis is placed on immune checkpoint pathways, which normally serve as regulatory mechanisms that prevent excessive or inappropriate immune activation. Tumors can exploit these pathways to evade immune surveillance. Molecules such as PD-1, PD-L1, CTLA-4, and other inhibitory receptors and ligands can limit the activity of tumor-reactive T cells and other immune populations. Drugs that block these inhibitory signals have transformed the treatment of several cancers by restoring antitumor immune activity and, in a subset of patients, producing deep and durable clinical responses.

However, most sarcomas have not demonstrated the same degree of responsiveness to immune checkpoint blockade observed in cancers such as melanoma and certain lung, kidney, and other malignancies. Understanding the biological basis for this resistance is therefore a major focus of Dr. Llosa’s research. His work examines the composition, organization, and functional state of immune cells within sarcoma tumors, including T cells, B cells, macrophages, dendritic cells, and other components of the tumor microenvironment. The laboratory also studies immune structures and signaling pathways that may predict response to immunotherapy or represent new therapeutic targets.

Using approaches that integrate multiplex tissue imaging, flow cytometry, single-cell RNA sequencing, spatial transcriptomics, immune-receptor sequencing, molecular profiling, and translational laboratory models, Dr. Llosa’s research seeks to define the mechanisms that shape antitumor immunity across different sarcoma subtypes. These studies are designed not only to identify biomarkers of immune response and resistance, but also to generate rational combinations of immunotherapies with other treatments that can be translated into clinical trials.

The overarching objective of this research program is to develop more effective, durable, and biologically informed treatments for patients with sarcoma, particularly children and young adults with high-risk, relapsed, or metastatic disease. By bridging laboratory investigation with clinical research, Dr. Llosa aims to bring the long-lasting benefits achieved with immunotherapy in other cancers to a broader population of patients with sarcoma.

• Pediatric Oncology Program
• Sidney Kimmel Comprehensive Cancer Center

View all trials by this principal investigator.

• 1. Theilacker C., Coleman F.T., Mueschenborn S., Llosa N.J., Grout M., and Pier G.B. Construction and Characterization of a Pseudomonas aeruginosa Mucoid Exopolysaccharide Alginate Conjugate Vaccine. Infection and Immunity. 2003 Jul;71(7):3875-84.
  2. Pier G.B., Boyer D., Preston M., Coleman F.T., Llosa N.J., Mueshenborn- Koglin S., Theilacker C., Goldenberg H., Uchin J, Priebe G.P., Grout M, Posner M, Cavacini L. Human Monoclonal Antibodies to Pseudomonas aeruginosa Alginate That Protect against Infection by both Mucoid and Nonmucoid strains. The Journal of Immunology. 2004. Nov; 173: 5671-5678.
  3. Nicolas Llosa MD, Carmina Erdei Grozavescu MD. A teen with persistent painful papules and plaques” - Contemporary Pediatrics Journal, September 1, 2009 issue
  Llosa, Nicolás José
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  4. Llosa NJ, Campodónico VL, Grout M, Doring G, Maira-Litrán T, Pier GB.Evaluation of Flagella versus Flagellin of Pseudomonas aeruginosa as Vaccines” Infect. Infection and Immunity. 2010 Feb; 78(2):746-755.
  5. Campodónico VL, Llosa NJ, Bentancor L, Maira-Litrán T, Pier GB.Infection and Immunity. Efficacy of a conjugate vaccine containing polymannuronic acid and flagellin against experimental Pseudomonas aeruginosa lung infection in mice. Infection and Immunity. 2011 Aug;79(8):3455-64
  6. Llosa NJ, Geis AL, Thiele-Orberg E, Housseau F. Interleukin-17 and type 17 helper T cells in cancer management and research –ImmunoTargets and Therapy - March 2014 Volume 2014:3 Pages 39—54
  7. Llosa NJ, Cruise M, Tam A, Wick EC, Hechenbleikner EM, Taube JM, Blosser L, Fan H, Wang H, Luber B, Zhang M, Papadopoulos N, Kinzler KW, Vogelstein B, Sears CL, Anders RA, Pardoll DM, Housseau F. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints - Cancer Discovery. 2014 Oct 30. pii: CD-14-0863
  8. Dejea C, Wick E, Hechenbleikner E, White J, Welch JM, Rossetti B, Peterson S, Snesrud E, Borisy G, Lazarev M,Stein E, Vadivelu J, Roslani A, Malik A,Wanyiri J, Fu K, Wan F, Goh KL, Llosa NJ, Housseau F, Katherine R, Vogelstein B, Kinzler K, Pardoll D, Sears C. Microbiota organization rather than composition is an underlying feature of many colorectal cancers" -; PNAS Nov. 2014