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Table of Contents
LETTER TO EDITOR
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 593-594

Evolving immunotherapy approaches and their efficacy based on gender of the patient: A reflection


Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre, Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India

Date of Submission27-Jul-2021
Date of Decision01-Aug-2021
Date of Acceptance08-Aug-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
Kuraparthy Sambasivaiah
Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre, Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_175_21

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How to cite this article:
Sambasivaiah K, Sansar B. Evolving immunotherapy approaches and their efficacy based on gender of the patient: A reflection. Cancer Res Stat Treat 2021;4:593-4

How to cite this URL:
Sambasivaiah K, Sansar B. Evolving immunotherapy approaches and their efficacy based on gender of the patient: A reflection. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:593-4. Available from: https://www.crstonline.com/text.asp?2021/4/3/593/327770



We read with interest the article titled, “Impact of sex of the patient on efficacy and safety of cancer immunotherapy: A retrospective audit,”[1] and the editorial by Khaddar and Mishra.[2] In this study, the authors explored a possible association between immunotherapy-based treatment outcomes and gender of the patients. No differences were found.

The effect of gender on immune responses has been widely documented.[3] In a comprehensive meta-analysis by Conforti et al., male patients were found to have a significantly better survival compared to female patients treated with immunotherapy regimens.[4] However, another large meta-analysis by Wallis et al. found no such differences in outcomes according to gender.[5] Conforti et al. refined their meta-analysis and showed that female patients derived a greater benefit from a combination of immunotherapy and chemotherapy compared to male patients.[6] They attributed the lack of difference reported in the Wallis et al.'s meta-analysis to the inclusion of four randomized controlled trials of immunotherapy and chemotherapy combinations with female patients deriving a greater benefit in those.

Analyzing these data, Wang et al. made an intriguing and provocative observation that the tumors in men are likely to be more antigenic and hence likely to have superior responses to immunotherapy alone, whereas women having better adaptive and innate immunities respond better to the combination of chemotherapy and immunotherapy.[7]

In the present study, female patients were underrepresented. In addition, the data on patients receiving a combination of immunotherapy and chemotherapy were missing. Further, this study cohort did not include data on the use of CTLA-4 inhibitors, which comprised a substantial part of the earlier meta-analyses. These could be some of the reasons why the present study failed to detect any impact of gender on outcomes.

The authors have also explored the interaction of antibiotic use and concomitant steroid use and their implications, which is interesting considering the effects of these on the gut microbiome and the recent insights on their immunomodulatory effects.[8]

Interestingly, in the present study, pneumonitis was more commonly seen in male patients compared to female patients. As the authors have noted, the relatively small number of female patients was a limitation for drawing conclusions on efficacy and toxicity. Furthermore, smoking could be a confounding factor.

The issue of the effect of gender on outcomes in cancer immunotherapy needs urgent clinical attention and investigation, to develop optimal management strategies for men and women alike.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kapoor A, Noronha V, Patil VM, Joshi A, Menon N, Mahajan A, et al. Impact of sex of the patient on efficacy and safety of cancer immunotherapy: A retrospective audit. Cancer Res Stat Treat 2021;4:238-43.  Back to cited text no. 1
  [Full text]  
2.
Khaddar S, Mishra BK. Biomarkers for response to immune checkpoint inhibitors: Where do we stand? Cancer Res Stat Treat 2021;4:363-4.  Back to cited text no. 2
  [Full text]  
3.
Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016;16:626-38.  Back to cited text no. 3
    
4.
Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G, et al. Cancer immunotherapy efficacy and patients' sex: A systematic review and meta-analysis. Lancet Oncol 2018;19:737-46.  Back to cited text no. 4
    
5.
Wallis CJ, Butaney M, Satkunasivam R, Freedland SJ, Patel SP, Hamid O, et al. Association of patient sex with efficacy of immune checkpoint inhibitors and overall survival in advanced cancers: A systematic review and meta-analysis. JAMA Oncol 2019;5:529-36.  Back to cited text no. 5
    
6.
Conforti F, Pala L, Bagnardi V, Viale G, De Pas T, Pagan E, et al. Sex-based heterogeneity in response to lung cancer immunotherapy: A systematic review and meta-analysis. J Natl Cancer Inst 2019;111:772-81.  Back to cited text no. 6
    
7.
Wang S, Cowley LA, Liu XS. Sex differences in cancer immunotherapy efficacy, biomarkers, and therapeutic strategy. Molecules 2019;24:E3214.  Back to cited text no. 7
    
8.
Rangarajan B, Abhinav RK. Beyond the tumor and tumor milieu-Factors affecting responses to immunotherapy. Cancer Res Stat Treat 2019;2:224-5.  Back to cited text no. 8
  [Full text]  




 

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