Immunomodulation, which has demonstrated significant promise in multiple other GU malignancies, has not been as effective in the treatment of PCa. However, as we continue to learn more about the immune system’s interactions with cancer cells, novel therapies targeting new pathways emerge.
More recently, a novel, immunosuppressive B cell subpopulation which accelerated the emergence of castrate resistant prostate cancer (PCa) was discovered in mouse models and PCa patients. Targeting B lymphocytes with an anti-CD20 antibody in the mouse models delayed regrowth of PCa. Based on this translational background, the authors hypothesized that neoadjuvant treatment of high risk PCa patients with the anti-CD20 immunotherapy, Rituximab, would significantly reduce B cell infiltration of prostate tumors. This was an open label, non-randomized, single arm clinical trial for high risk PCa prior to prostatectomy (“PROTUX” NCT01804712). Subjects were candidates for prostatectomy with curative intent. Enrolled men received one cycle of rituximab (375 mg/m2 IV once weekly for 28 days), followed in 2 weeks by prostatectomy. Controls were selected from a pathologic biobank with similar patient characteristics and stained concurrently for CD20. Rituximab is an established agent used for treatment of other malignancies, including lymphoma. In a prior study, they authors found that it did significantly reduce B-cell infiltration of prostate cancers in 8 patients with high risk PCa who received neoadjuvant rituximab when compared to 11 historical controls.1
In this abstract, the authors report analyses of T cell and immune checkpoint markers to determine how the reduction of B cell density in tumor tissue may have altered the immune environment. Specifically, they assessed CD20, CD3, CD8, PD1 and PD-L1 staining in the tumor regions of the RP specimens. Mean CD20 IHC stained area in the tumor region of the treated group was 0.027 (95% CI 0.021 – 0.033) and control was 0.044 (95% CI 0.028 – 0.062, p=0.02) utilizing unequal variances t test. The same approach was used to analyze CD3, CD8, PD1 and PD-L1 immunostaining and showed modification of different immune cell populations.
Based on this, the authors conclude that using neoadjuvant rituximab significantly decreased B cell density within tumors compared to historical controls (p=0.02, relative to controls) and appeared to alter the immune environment within the tumor region. These results provide evidence that rituximab can modify the immune environment of the tumor.
However, the clinical impact of neoadjuvant rituximab has not yet been reported. We look forward to those results.
Presented By: Stephen T. Ryan, MD1
Co-Author(s): Michael Liss2; Ahmed Shabaik1; Emily Pittman1; Jing Zhang1; Michelle Muldong1; Danielle Burner1; Jonathan Cunha, MS1; Nicole Basler, MS1; Shabnam Shalapour1; Michael Karin1; Karen Messer1; Stephen Howell1; Christopher Kane1 and Christina Jamieson1
Institution(s):
- University of California San Diego, La Jolla, CA
- Dept of Urology, University of Texas Health Science Center San Antonio, San Antonio, TX
Woo JR, Liss MA, Muldong MT, Palazzi K, Strasner A, Ammirante M, Varki N, Shabaik A, Howell S, Kane CJ, Karin M, Jamieson CA. Tumor infiltrating B-cells are increased in prostate cancer tissue. J Transl Med. 2014 Jan 30;12:30. doi: 10.1186/1479-5876-12-30.
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @TjuUrology, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona