Table 1.

Therapeutic and preventive approaches successfully used or potentially can be implemented to prevent primary immunodeficiency-associated cancer hallmarks.

Hallmark or Process	Agent or Vause	Drug or Modality
Avoiding immune destruction	EBV infection**	EBV-specific cytotoxic T lymphocytes
	Costimulatory agonist	Anti-GITR, anti-ICOS, anti-OX40, and anti-CD27
	Regulatory T cells**	Anti-CD25
Deregulating cellular energetics	Immunometabolism	IDO1 inhibitors, A2AR antagonists, Arginase inhibitors, and Glutaminase inhibitors
Evading growth suppressors	Dual checkpoint blockade*	Anti-CTLA-4 (Ipilimumab), anti-PD1 (Nivolumab), anti-PDL1 (Atezolizumab), anti-TIM3, anti-LAG3, anti-TIGIT, and anti-VISTA
Genome instability and mutation	DNA repair defect*	Decrease radiation exposure
	Epigenetic changes*	DNMT inhibitors and HDAC inhibitors
Inducing angiogenesis	RAS-associated autoimmune leuko-proliferative disease	Cetuximab, Pantitumumab, and Bevacizumab
Sustaining proliferative signaling	EBV infection**	Butyrate and Ganciclovir
	HPV infection*	L1 virus-like particles vaccine
	BTK activation*	Ibrutinib and Acalabrutinib
	PI3K activation**	Rifampicin, Buparlisib, Alpelisib, Nemiralisib, and Idelalisib
	PI3K or NFKB activation**	Rituximab, Ibritumomab Tiuxetan, and Tositumomab
	mTOR activation**	Everolimus
	MAPK/ERK activation**	Trametinib
	Stem cell and myeloid development defects	Bone marrow transplantation, CSF1R inhibitor, and HDAC inhibitors class IIa
	Cytokines	JAK inhibitors, TGF inhibitors, and MET inhibitors
Tumor-promoting inflammation	H. pylori infection*	Standard triple therapy consisting of proton pump inhibitor, clarithromycin, and amoxicillin
	Chronic inflammation*	Nonsteroidal anti-inflammatory drugs

EBV, Epstein–Barr virus; GITR, glucocorticoid-induced TNFR-related protein; ICOS, Inducible T-cell COStimulator; IDO1, Indoleamine 2;3-dioxygenase 1; A2AR, Adenosine 2A receptor; CTLA4, Cytotoxic T-lymphocyte protein 4 precursors; TIM3, T-cell immunoglobulin and mucin domain 3; LAG3, Lymphocyte-activation protein 3; TIGIT, T-cell Immunoreceptor With Ig And ITIM Domains; VISTA, V-domain Ig suppressor of T-cell activation; DNMT, DNA Methyltransferase; HDAC, Histone deacetylase; HPV, human papillomavirus; PI3K, Phosphoinositide 3-kinase; CSF1R, Colony-stimulating factor 1 receptor; NFKB, nuclear factor kappa B; JAK, Janus kinase; TGF, Transforming growth factor.

**Genes/pathways very important in the pathogenesis of antibody deficiencies.

*Genes/pathways important in the pathogenesis of antibody deficiencies.