Let's immune system help

Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido, 
Vinod P Balachandran, et al. Nature Medicine17 (2011) 


I would like to hilight this paper to our readership, as many of your are involved in the design of clinical trials and selection of potential biomarkers. This report is one of a handful of high impact papers that report the coperative role that inflammatory infiltrate and non cell autonomous effectors play in modulating response to established agents. This study demonstrates an interesting immunological mechanism of Imatininb  that contributes to the antitumor effect in a Gastrointestinal Stromal Tumor (GIST) mouse model. Inflammatory infiltrate is a known finding in GIST specimens (including intratumoral CD8+ Tcells, Treg cells and macrophages). Acording to the authors, Imatinib activates CD8+ T cells and induces Treg cells apoptosis within the tumor. Imatinib is therefore able to reduce the expression of 2,3-dioxygenase (Ido) of tumor cells. Ido enzyme is involved in the catayzation of immunosuppressive metabolites from tryptophan and therefore mediates downstream immunological response. Interestingly Imatininb resistant tumors, generally as a result of a second KIT mutation, restore the overexpression of IDO and combination of Imatinib with CTLA-4 blockade (a well established immunotherapeutic strategy) act synergistically. This insight provides some hints on something we have been suspecting for a long time. It is easy to predict consequences for rational design of combination therapies and strategies to overcome resistance in Imatinib resistant tumors.

Interdisciplinary approach to cancer patients: time to measure the evidences

Why am I publishing this post? Because still a small percentage of patients is treated in Comprehensive Cancer Centers. Although, that is not the only kind of place a patient can receive multidisciplinary care, I assume this is at least partially true. How can we account for the advantages of "personalized" treatment, due to multistep re-evaluation of the case?

Several reports tell us interdisciplinary approach may save months to our patients, especially the most challenging ones (such as pancreatic cancer), or during the most delicate phase of their disease (unclear therapeutic options, multifocal or metastatic disease). If a treatment gives you a 10% better event free survival, wouldn't you feel obliged to test it and eventually offer it to every one?

http://www.ncbi.nlm.nih.gov/pubmed/21941491

Case Rep Oncol. 2011 May;4(2):413-419. Epub 2011 Aug 24.

Long-Term Relapse-Free Survival by Interdisciplinary Collaboration in a Patient with Metastatic Pancreatic Cancer (UICC IV).

Roehrig S, Wein A, Albrecht H, Maennlein G, Wolff K, Muskoski D, Amann K, Janka R, Hohenberger W, Hahn EG, Siebler J, Neurath MF, Boxberger F.

Source

Department of Internal Medicine 1, University of Erlangen, Erlangen, Witten, Germany.

Abstract

INTRODUCTION:

The prognostic outlook for patients suffering from pancreatic cancer is generally poor. Particularly in cases of advanced and metastatic disease, long-term relapse-free survival may be achieved only in a few cases.

CASE REPORT:

A 45-year-old patient presented with metastatic pancreatic cancer. Liver metastases had been intra-operatively confirmed by histology. Prior to initiating treatment, a portacath was surgically implanted. Subsequently, the patient received a weekly dose of 1,000 mg/m(2) gemcitabine combined with 2,000 mg/m(2) high-dose 5-fluorouracil as a 24-hour infusion for palliative treatment. As the patient was suffering from a stenosis of the ductus hepaticus communis, an endoprosthesis was primarily implanted. After 18 applications of chemotherapy during which only low toxic side effects such as nausea, vomiting and alopecia (NCI-CTC grade 1) presented, a partial remission of the primary tumor was observed. In the course of chemotherapy treatment, the carbohydrate antigen 19-9 tumor marker value normalized. Thus, the interdisciplinary tumor board of the University of Erlangen decided to perform a laparoscopy to evaluate the status of liver metastases after palliative chemotherapy treatment. Subsequently, the primary tumor could be completely resected (pT2, pN0, pM0, L0, V0, G2, R0); liver metastases were not observed. Eight years after the initial diagnosis, the patient is relapse-free, professionally fully integrated and presents with an excellent performance status.

CONCLUSION:

Patients suffering from metastatic pancreatic cancer may benefit from treatment combinations with palliative intent. In singular cases, patients may even have a curative treatment option, provided a close interdisciplinary collaboration exists.