**Author details**

**5.4. Possible combination DCs and other approaches**

188 Multiple Myeloma - A Quick Reflection on the Fast Progress

CD25+

completely rejected [108]. An increased number of CD4+

enhance the efficacy of tumor vaccine in the future.

the specific depletion of CD4+

**6. Future perspectives**

**Acknowledgements**

on tumors.

In the presence of regulatory and suppressive environment, it is very difficult to elicit or induce effective immune response after DC vaccination in cancer patients. To improve the clinical outcomes, DC vaccines need to be combined, in particular for patients at advanced stages, with other approaches that offset the suppressive tumor environment [107]. It has been known that

of the anti-tumor immune response of tumor-bearing animals, although the tumors are not

been demonstrated in patients with MM [22, 109]. Depletion of Treg may have resulted in improved response to tumor vaccine in animal models and a clinical study. In addition, blocking antibodies or soluble receptors were exploited for the blockade of suppressive cytokines in the tumor microenvironment, such as IL-10 [110], IL-13 [111], TGF-β [112] and VEGF [113]. Such strategies can be used to block immune-inhibitory signals in lymphocytes as illustrated by anti-CTLA-4 [114] and/or anti-PD1 [115] or to block their ligands expressed

Another strategy to improve DC vaccination is combination approach with other immune cells, including adoptive T cells or NK cells. In adoptive T-cell transfer, one can seek to modulate the number of regulatory T cells, and transfer a population of activated effector cells. The combination of DC vaccination and adoptive T-cell transfer led to a more robust antitumor response than the use of each treatment modality [116]. These findings illuminate a new potential application for DC vaccination in the *in vivo* stimulation of adoptively transferred T cells. Therefore, combining active and passive immunotherapies in the treatment of MM may

Progress in understanding DC biology in MM patients and the recruitment of suppressive cells of the adaptive and innate immune system in antitumor immunity of cellular immunotherapy is leading to new concept which aims at improved immune and clinical outcomes in MM. The new generation of DCs may be a potential vaccine therapy for inducing the rate of tumor responses and prolonging survival of patients with MM. Furthermore, information from studies that combine DC vaccine with other therapies, including chemotherapy, radiation therapy, molecular target agents, other immunotherapy (adaptive T cells or NK cells), or adjuvants will have high impact on enhancing therapeutic immunity in MM by simultaneously enhancing the potency of immune responses and offsetting immunoregulatory pathways.

This study was financially supported by grant no. 2011-0005285 from General Researcher Program Type II of the National Research Foundation of Korea; grant no. RTI05-01-01 from

Treg cells by anti-CD25 antibodies increases the efficiency

FoxP3+

regulatory T cells have

CD25+

Je-Jung Lee1,2,3, Youn-Kyung Lee3 , Hyun Ju Lee1,2, Sung-Hoon Jung1,2 and Thanh-Nhan Nguyen-Pham1,2

1 Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea

2 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea

3 Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea

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**Chapter 10**

**Novel Prognostic Modalities in Multiple Myeloma**

The therapy for multiple myeloma has made major strides over the last 15 years, by and large due to the advances in molecular biology and the focus on patient-oriented translational investigations. Although the survival outcomes have improved significantly, clinical features such as older age, renal insufficiency at diagnosis, primary plasma cell leukemia and extramedullary disease remain major therapeutic challenge. The explosion of data from all the clinical, genomic and proteomic investigations has also made it difficult to assimilate all the information and translate it effectively for clinical practice. Although multiple myeloma is still considered by most though leaders as an incurable but treatable disease, the development of novel diagnostic and therapeutic modalities are bringing optimism of potential curability dream of being curable. Over the last decade, new biologic markers and novel imaging modalities have been explored in the context of clinical trials. The present chapter will attempt to summarize these data and propose how to incorporate this knowledge in current clinical

The Durie-Salmon Staging (DSS) system [1] was developed as a prognostic model almost four decades ago when the standard of care for myeloma was oral melphalan and prednisone. Over the years, DSS has stood the test of time as a reasonable assessor of disease burden even in the era of novel agents. The major the drawback of the DSS was that it does not account for the biologic variability of disease even in patients with comparable disease burden. The Interna‐

> © 2013 Boota et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

Mariam Boota, Joshua Bornhorst, Zeba Singh and

Additional information is available at the end of the chapter

Saad Z. Usmani

**1. Introduction**

practice.

**2. Laboratory & pathology tools**

**2.1. Durie-Salmon staging and the international staging system**

http://dx.doi.org/10.5772/55965

