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.