2014: The Year of Immunotherapy in Sarcoma?

Drs. Pollack and Jones

For those reading the headlines in the New York Times, 2013 was the year when immunotherapy began "breaking through cancer’s shield.1” Indeed, this year it seemed that high impact publication after publication, in the most prestigious journals, demonstrated incontrovertible evidence of the power of immunomodulatory checkpoint inhibitors and cellular therapies to lengthen and improve the lives of cancer patients.2-6 These incredible strides build on momentum that has been growing for years throughout the oncology world, advancing the care of malignancies as diverse as melanoma, lung cancer, prostate cancer, renal cell carcinoma and leukemia.5, 7-11

However, in the sarcoma world, you may not have realized that we are living amidst a revolution. Of the 209 posters at the 2013 Connective Tissue Oncology Society (CTOS) Meeting, only 4 (1.9%) were immunotherapy related. Of the 40 articles published by the journal Sarcoma in 2013, only one12 was immunotherapy related and none of the articles in 2012 had an immunotherapy focus.

We were particularly disappointed since it seemed 2011 was a year that sarcoma world had turned the corner. The American Society of Clinical Oncology (ASCO) that year had a sarcoma immunotherapy special panel and a landmark study published by the NCI surgery branch demonstrated that NY-ESO-1 specific T cells can mediate tumor regression in patients with synovial sarcoma.13 However, sarcoma’s immunotherapy efforts seem to be losing steam as progress in almost every other type of cancer seems to be speeding up.

A lack of clear progress is not only a setback for the sarcoma community, but a potential loss for cancer therapeutics as a whole. As we have repeatedly seen in the world of molecular biology, the diversity of sarcomas offers the scientific world a unique opportunity to understand fundamental problems in oncology and can potentially lead to broad advances in cancer therapeutics. The same may be true in the field of immunotherapy. For example, synovial sarcoma and myxoid/ round cell liposarcoma consistently express NY-ESO-1, one of the most immunogenic cancer proteins, in a homogenous fashion not seen in any other malignancy.14,15 We have been trying to elucidate how these subtypes may evade the natural immune response so that we can better apply techniques for culturing NY-ESO-1 specific T cells.16

Not all sarcomas will express immunogenic targets with the consistency and homogeneity of synovial sarcoma and myxoid/ round cell liposarcoma, but individual sarcoma tumors are likely to express any one of a number of individualized target profiles which further research could better define.17 There has been a lot of discussion lately about how best to approach "personalized medicine;" immunotherapy may bolster the molecularly personalized approaches that on their own have disappointed some.18 By developing a cadre of immunotherapeutic modalities, we hope to someday tailor a mix of targeted immunotherapeutic agents and checkpoint inhibitors to eradicate an individual patient’s cancer.

However, these approaches will not develop by themselves. It has taken 30 years for immunotherapy to arrive at this point and the other disease groups have an undeniable head start. We need to develop sarcoma specific immunotherapeutic strategies from target identification, to a better characterization of the microenvironment as well as practical strategies for moving these new therapies to the clinic. The pharmaceutical industry is frequently skeptical of supporting clinical trials in sarcoma so we need to be proactive in producing research that clearly demonstrates where these strategies are likely to be successful.

As we know too well, cancer research takes time. If we want immunotherapies to benefit sarcoma patients in the future, we need to start now. We should all make 2014 the year of sarcoma immunotherapy.


This article is an opinion piece and has not been peer-reviewed.
Last revised January 2014.

by Seth M Pollack, MD
Robin L. Jones, MB, BSc, MD (Res), MRCP
Medical Oncology
Fred Hutchinson Cancer Research Center and the University of Washington
Seattle, Washington


1. Kolata G. Breaking Through Cancers Sheild. The New York Times 2013.
2. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013;369:134-44.
3. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122-33.
4. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368:1509-18.
5. Chapuis AG, Ragnarsson GB, Nguyen HN, et al. Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med 2013;5:174ra27.
6. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013;5:177ra38.
7. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011;365:725-33.
8. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363:411-22.
9. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366:925-31.
10. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26.
11. Dudley ME, Gross CA, Somerville RP, et al. Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol 2013;31:2152-9.
12. Maki RG, Jungbluth AA, Gnjatic S, et al. A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma. Sarcoma 2013;2013:168145.
13. Robbins PF, Morgan RA, Feldman SA, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011;29:917-24.
14. Pollack SM, Jungbluth AA, Hoch BL, et al. NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. Cancer 2012.
15. Jungbluth AA, Antonescu CR, Busam KJ, et al. Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7. Int J Cancer 2001;94:252-6.
16. Pollack SM JR, Farrar E, Lee SM, Cao J, Pillarisetty VG, Heimfeld S, Gullet A, Conrad EU, Eary J, Warren EH, Jarstens J, Riddell SR, Yee C. Tetramer Guided Cell Sorter Assisted Production of NY-ESO-1 Specific Cells for the Treatment of Synovial Sarcoma and Myxoid Round Cell Liposarcoma. Connective Tissue Oncology Society Meeting 2013.
17. Pollack SM, Loggers ET, Rodler ET, Yee C, Jones RL. Immune-based therapies for sarcoma. Sarcoma 2011;2011:438940.
18. Thomas D. Personalized Medicine for Sarcoma: Have we lost perspective? ESUN 2013;10.

Continuing the Discussion on Immunotherapy in Sarcoma

Since publishing our editorial in ESUN we have gotten a tremendous response. We are truly heartened to realize that there is so much optimism and hope in the sarcoma community regarding the promise of scientific research including immunotherapy research to bring new treatments to sarcoma patients. We have also received a number of inquiries from patients regarding so called “immunotherapies” which are not evidenced based or grounded in firm science even though they claim to be. Some of these are naturopathic remedies that are harmless, though we think the evidence to suggest that they will benefit patients is slim at best.

However, there are other centers purporting to offer “immunotherapy” that are out-right frauds. These “centers” put scientific appearing information on their website and sometimes even links to peer reviewed published literature, that actually are not even relevant to the treatments that they offer. The websites for these so-called foundations frequently have testimonials posted proclaiming amazing responses, though a close reading of the fine print reveals that not all of the important information about these patients is disclosed. I know of one patient that spent over $100,000 of her savings at one of these foundations. As would be expected, her cancer progressed in spite of this so-called “immunotherapy.”

We strongly urge all patients to be skeptical of any organization that claims to have found cancer treatments not accepted by the scientific community. If these groups have such convincing stories, they should publish case reports in the peer reviewed literature. If they have treated many individuals, they should publish their complete data sets and demonstrate the efficacy of their treatments to the scientific community.

While we certainly have disagreements with insurance companies about what specific treatments should be reimbursed in specific instances, it can also be instructive if your insurance company denies an expensive cancer treatment and your doctor is either unwilling or unable to overcome the denial. This may be a red flag that there is inadequate data to support this treatment. A well designed study at a reputable center will generally not accept payment for the investigational aspects of their study and will only charge you or your insurance company for things that would have been done if you were receiving a standard of care treatment (for example, doctor’s visits, labs, CT scans etc).

Although we are probably the some of the biggest advocates for immunotherapy research in sarcoma, we are also the first to admit there is no proven benefit of any immunotherapy in sarcoma at this point. The research is very promising. When possible, we strongly recommend participation is well-designed immunotherapy trials at major academic medical centers. If you have questions about specific treatments, seek consultation with an oncologist at one of these centers with a specific focus on sarcoma. These physicians are the best people to ask about treatments that you hear about or read about on the web and they are the people who are most likely to know about the exciting trials we hope will soon be opening around the country.