|Year : 2019 | Volume
| 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 Submission||01-Jul-2019|
|Date of Acceptance||08-Jul-2019|
|Date of Web Publication||22-Aug-2019|
Dr. Joud Hajjar
Baylor College of Medicine, Texas Children Hospital, Houston, TX
Source of Support: None, Conflict of Interest: None
|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  and a 3–14-fold increase in relative risk of developing autoimmunity. Within PID, patients with common variable immunodeficiency have a 9-fold increase in developing lymphoma. HIV-infected patients have a 77-fold increased risk of developing non-Hodgkin's lymphoma  and a 28-fold higher risk of autoimmune hemolytic anemia. Organ transplant recipients have a 2–3-fold higher risk for malignancy compared to the general population with the same age and sex. 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.,
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?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, and Daher et al. describe neuromuscular weakness syndromes observed in a series of patients treated with immune checkpoint inhibitors. By querying the Food and Drug Administration's side effect database, Pundole et al. report on iRAEs in patients treated with cancer immunotherapy. Al Salihiet al . describe cutaneous malignancies in a case series of patients with primary and secondary immunodeficiencies. Finally, this special issue highlights some of the ongoing clinical trials to assess the safety and efficacy of immunotherapy in immunocompromised patients , 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.
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