. 2022 Jul 4;25(8):104717. doi: 10.1016/j.isci.2022.104717

Table 1.

Completed studies in humans describing the effects of ADT on immunity

ADT Regimen	N	Compartment	Patient population or disease	Time on ADT	Method	Findings	Study
LHRH agonist	12	Peripheral blood	Metastatic prostate cancer	28 days	Flow	↑: lymphocytes	Oliver et al. (1995)
LHRH agonist	16	Peripheral blood	Node-positive localized prostate cancer initiation ADT prior to radiation	4 months	Flow, RT-PCR	↑: total lymphocytes, total T cells, CD4⁺ T cells, naive CD4⁺ T cells, naive CD8⁺ T cells, memory CD8⁺ T cells, NK cells, naive CD4+TREC + cells. Naive: memory CD4⁺ T cells Unchanged: B cells, Ki-67 CD4⁺ or CD8⁺ T cells	Sutherland et al. (2005)
LHRH agonist with melanoma vaccine	33	Peripheral blood	Stage IIb-IV melanoma	6 months	Flow, RT-PCR, ELISA	Unchanged: vaccine peptide-specific T cells, TREC, cytokines, or T regulatory cells	Vence et al. (2013)
LHRH agonist with allogeneic or autologous hematopoietic stem cell transplant (HSCT)	40	Peripheral blood	Hematologic malignancies undergoing allogeneic or autologous HSCT, investigating the effect of ADT on engraftment	4 months	Flow, RT-PCR, ELISA, TCR PCR	↑: neutrophils, lymphocytes, total and naive CD4⁺ T cells, TREC+CD4⁺ T cells, T cell receptor repertoire, peripheral T cell function Unchanged: CD8⁺ T cells, regulatory T cells, NK cells, gamma-delta T cells, cytokine production	Sutherland et al. (2008)
LHRH antagonist	4	Peripheral blood	Healthy males age 35–55	28 days	Flow	↑: NK cells Unchanged: total lymphocytes, CD4⁺ or CD8⁺ T cells, CD4+:CD8+ ratio, expression of NKG2D or CXCR1 ↓: CD4⁺CD25⁺ T cells, CD8⁺ T cell IFN-γ expression	Page et al. (2006)
AR antagonist +/− orchiectomy	61	Peripheral blood	Localized and metastatic prostate cancer	N/A	NK activity assay	Unchanged: NK cell activity	Kastelan et al. (1992)
AR antagonist +/− prostate cancer vaccine	38	Peripheral blood	Non-metastatic (M0) prostate cancer with biochemical failure after definitive therapy	3 months	Flow, RT-PCR, ELISA	↑: NK cells, mature NK cells, Tim3+ NK cells, naive T cells, TRECs Unchanged: VEGF ↓: MDSCs	Madan et al. (2021)
AR antagonist with estrogen	10	Peripheral blood	Transgender male to female	4 months	Flow, ELISA	↑: leukocytes, T_H1-associated chemokine receptors CCR1, CXCR3, CCR5 Unchanged: CD4⁺ T cells, CD8⁺ T cells, CD4:CD8 ratio, total lymphocytes, B cells, Ig levels ↓: NK cells	Giltay et al. (2000)
AR antagonist or CYP17A1 inhibitor	44	Peripheral blood	Metastatic castration resistant prostate cancer	3 months	Flow, Luminex	Unchanged: polymorphonuclear myeloid-derived suppressor cells	Pal et al. (2019)
LHRH agonist + AR antagonist + radiation	19	Peripheral blood	Localized prostate cancer	6 weeks	Flow	↑: CD4⁺ and CD8⁺ T cells Unchanged: B cells, NK cells	Johnke et al. (2005)
LHRH agonist plus AR antagonist or dexamethasone	22	Peripheral blood	Localized prostate cancer on adjuvant ADT	N/A	Flow	↑: CD14⁺HLA-DR^low/- monocytes, CD4⁺CD25⁺CD127^low/- Tregs Unchanged: B cells, CD4 T cells, or CD8 T cells	Vuk-Pavlović et al. (2010)
Bilateral orchiectomy	57	Peripheral blood	Locally advanced or metastatic prostate cancer	1 month	Flow	↑: CD8⁺ T cells ↓: CD4⁺ cells and CD4+:CD8+ ratio	Ma et al. (2020)
LHRH antagonist	15	Adipose tissue	Healthy males	1 month	Flow	↑: CD3⁺, CD4⁺, and CD8⁺ T cells, CD11c+ macrophages	Rubinow et al. (2017)
LHRH antagonist	29	Prostate cancer tissue	Localized prostate cancer	2 weeks	IHC, Nanostring	↑: CD8⁺ T cells and Tregs	Obradovic et al. (2020)
CYP17A1 inhibitor	44	Prostate cancer tissue	Localized prostate cancer	6 months	IHC	↓: CD8⁺ T cells	Calagua et al. (2017)
LHRH agonist + AR antagonist	26	Prostate cancer tissue	Localized prostate cancer	28 days	IHC, TCR PCR	↑: CD3 T cell, CD4 T cell, CD8 T cell, CD4:CD8, CD68 macrophage, CD83 dendritic cell	Mercader et al. (2001)
LHRH agonist + AR antagonist	6	Prostate cancer tissue	Localized prostate cancer	2 months	RNAseq, IHC	↑: CD8 T cells. Based on gene expression, increased immune cells infiltration and activity. Activation of antigen presentation, immune checkpoint, and IFN-γ signaling pathways Unchanged: gene fusions	Long et al. (2020)
LHRH agonist + AR antagonist	14	Prostate cancer tissue	Localized prostate cancer	3 months	H&E	↑: lymphocytes	Guinan et al. (1997)
LHRH agonist + AR antagonist or AR antagonist alone	35	Prostate cancer tissue	Localized prostate cancer	3 months	IHC	↑: CD3⁺ and CD8⁺ T cells, CD68⁺ macrophages Unchanged: CD20⁺ B cells, Foxp3+ lymphocytes, CD56⁺ NK cells	Gannon et al. (2009)