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Table of Contents
EDITORIAL
Year : 2019  |  Volume : 2  |  Issue : 3  |  Page : 53-54

Cancer immunotherapy for the immunosuppressed: Dissecting the conundrum of safety and efficacy


Department of Pediatrics, Section of Immunology, Allergy, and Retrovirology, Baylor College of Medicine, The William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston, TX, USA

Date of Submission01-Jul-2019
Date of Acceptance08-Jul-2019
Date of Web Publication22-Aug-2019

Correspondence Address:
Dr. Joud Hajjar
Baylor College of Medicine, Texas Children Hospital, Houston, TX
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIPO.JIPO_15_19

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How to cite this article:
Hajjar J. Cancer immunotherapy for the immunosuppressed: Dissecting the conundrum of safety and efficacy. J Immunother Precis Oncol 2019;2:53-4

How to cite this URL:
Hajjar J. Cancer immunotherapy for the immunosuppressed: Dissecting the conundrum of safety and efficacy. J Immunother Precis Oncol [serial online] 2019 [cited 2019 Nov 13];2:53-4. Available from: http://www.jipoonline.org/text.asp?2019/2/3/53/265154



One of the most critical functions of the immune system is surveillance, a mechanism by which the immune system detects precancerous and cancerous cells and eliminates them without further treatment. Failure of immune surveillance can lead to the development of malignancy. Cancer immunotherapy reprograms the immune system to target malignant cells that were able to escape immune surveillance. In the past decade, the world has witnessed favorable responses in different types of cancers treated with immunotherapy. However, reprogramming the immune system to target cancer cells is not without collateral damage. By activating the immune system directly or by removing the brakes of an antitumor response, immunotherapy may lead to aberrant activation of immune cells against self-antigens, causing unique adverse events termed “immune-related side effects (iRAEs).”

Patients with primary and secondary immunodeficiencies represent a unique population who are inherently at a higher risk for developing autoimmunity and malignancy. The relative risk is dependent on the underlying immunodeficiency, type of autoimmunity, and cancer. For example, patients with inborn errors of immunity (i.e., primary immunodeficiency [PID]) have a 1.42-fold increased risk in developing malignancy compared to the age-adjusted population [1] and a 3–14-fold increase in relative risk of developing autoimmunity.[2] Within PID, patients with common variable immunodeficiency have a 9-fold increase in developing lymphoma.[1] HIV-infected patients have a 77-fold increased risk of developing non-Hodgkin's lymphoma [3] and a 28-fold higher risk of autoimmune hemolytic anemia.[4] Organ transplant recipients have a 2–3-fold higher risk for malignancy compared to the general population with the same age and sex.[5] This significant risk increase in malignancy is due to tumor cell escape and lack of proper immunosurveillance caused by the underlying immunodeficiency. The increased risk of autoimmunity might be due to several mechanisms, such as failure of central tolerance, defects in the immune-mediated clearance, apoptosis defects, formation of autoantibodies, or aberrant innate immune responses.[6],[7]

Using cancer immunotherapy in patients with primary and secondary immunodeficiencies is explicitly challenging. In addition to the known risk of immunotherapy in general cancer patients, there have been concerns about the safety and efficacy of immunotherapy in immunodeficient patients. Key questions are: Will cancer immunotherapy be effective when the baseline immune system is compromised?[8]Will this therapy lead to further immune dysregulation in those patients who are already at higher risk for autoimmunity? The data available on safety and efficacy of treating immunocompromised patients with cancer using immunotherapy are limited. Many of the clinical trials tend to exclude patients with preexisting immunodeficiency, and many of those patients are undertreated, underdosed, or they have an early interruption of their treatment due to the perceived concern of side effects.

This special issue aims to bridge some of the knowledge gaps in using immunotherapy to treat cancer in patients with immunodeficiency and autoimmunity. Shahet al . describe the safety of immune checkpoint inhibitors in patients with preexisting autoimmune disorders,[9] and Daher et al. describe neuromuscular weakness syndromes observed in a series of patients treated with immune checkpoint inhibitors.[10] By querying the Food and Drug Administration's side effect database, Pundole et al. report on iRAEs in patients treated with cancer immunotherapy.[11] Al Salihiet al . describe cutaneous malignancies in a case series of patients with primary and secondary immunodeficiencies.[12] Finally, this special issue highlights some of the ongoing clinical trials to assess the safety and efficacy of immunotherapy in immunocompromised patients [13],[14] and advocates further research to fill the unmet need for such a vulnerable patient population.

Financial support and sponsorship

The author disclosed no funding related to this article.

Conflicts of interest

The author disclosed no conflicts of interest related to this article.



 
  References Top

1.
Mayor PC, Eng KH, Singel KL,et al . Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry. J Allergy Clin Immunol 2018;141:1028-35.  Back to cited text no. 1
    
2.
Fischer A, Provot J, Jais JP,et al . Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol 2017;140:1388-93.  Back to cited text no. 2
    
3.
Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 2011;103:753-62.  Back to cited text no. 3
    
4.
Yen YF, Lan YC, Huang CT, et al. Human immunodeficiency virus infection increases the risk of incident autoimmune hemolytic anemia: A population-based cohort study in Taiwan. J Infect Dis 2017;216:1000-7.  Back to cited text no. 4
    
5.
Chapman JR, Webster AC, Wong G. Cancer in the transplant recipient. Cold Spring Harb Perspect Med 2013;3. pii: a015677.  Back to cited text no. 5
    
6.
Todoric K, Koontz JB, Mattox D, et al. Autoimmunity in immunodeficiency. Curr Allergy Asthma Rep 2013;13:361-70.  Back to cited text no. 6
    
7.
Grimbacher B, Warnatz K, Yong PF, et al. The crossroads of autoimmunity and immunodeficiency: Lessons from polygenic traits and monogenic defects. J Allergy Clin Immunol 2016;137:3-17.  Back to cited text no. 7
    
8.
Spitzer MH, Carmi Y, Reticker-Flynn NE,et al . Systemic immunity is required for effective cancer immunotherapy. Cell 2017;168:487-5.  Back to cited text no. 8
    
9.
Shah M, Jizzini MN, Majzoub IE, et al. Safety of immune checkpoint blockate in patients with cancer and preexisiting auto immune diseases and/or chronic inflammatory disorders. J Immunother Precis Oncol 2019;2:59-64.  Back to cited text no. 9
    
10.
Daher A, Matsuoka CK, Loghin ME, et al. Neuromuscular weakness syndromes from immune checkpoint inhibitors: A case series and literature review. J Immunother Precis Oncol 2019;2:93-100.  Back to cited text no. 10
    
11.
Pundole XN, Sarangdhar M, Suarez-Almazor ME. Rheumatic and musculoskeletal adverse events with immune checkpoint inhibitors: Data from the food and drug administration adverse event reporting system. J Immunother Precis Oncol 2019;2:65-73.  Back to cited text no. 11
    
12.
Al Salihi S, Mejbel HA, Prieto VG, et al. Common cutaneous neoplasms in patients with immunodeficiency: A case series. J Immunother Precis Oncol 2019;2:79-84.  Back to cited text no. 12
    
13.
Granwehr BP. Immunocompromised hosts and cancer-HIV and immunotherapy. J Immunother Precis Oncol 2019;2:85-92.  Back to cited text no. 13
    
14.
Scilla KA, Russo A, Rolfo C. Immunotherapy use in Human Immunodeficiency Virus (HIV)-infected non-small cell lung cancer patients: Current data. J Immunother Precis Oncol 2019;2:55-8.  Back to cited text no. 14
    



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