Table 3.

Therapeutic effects on ER stress and tumor immunity.

Therapy	Tumor types	Mechanisms of action	Effects on ER stress/ERAD	References
Camptothecin	Leukemia	Cytotoxic therapy, targeting topoisomerase and inducing apoptosis but not ICD		Sauter et al. (2000), Obeid et al. (2007), and Tesniere et al. (2010)
Etoposide	Testicular cancer, lung, lymphoma, leukemia, neuroblastoma, and ovarian cancer	Cytotoxic therapy inducing apoptosis but not ICD	Promoting apoptosis in human hepatic stellate cells via ER stress induction	Sauter et al. (2000), Obeid et al. 2007), and Wang et al. (2016)
Mitomycin C	Adenocarcinoma of stomach and pancreas	Cytotoxic therapy inducing apoptosis but not ICD	Inducing ER stress	Sauter et al. (2000), Obeid et al. 2007), and Shi et al. (2013)
Cyclophosphamide	Lymphoma, leukemia, NSCLC, breast, and ovarian cancer	Cytotoxic therapy, high dose with immunosuppressive effects by inhibiting immune cell proliferation, while counteracting immunosuppression by Tregs in single low dose	Inducing ER stress to expose CRT and release HMGB1	Emadi et al. (2009), Schiavoni et al. (2011), Inoue and Tani (2014), and Ahlmann and Hempel (2016)
Cisplatin	Various types of cancers, such as breast, ovarian, testicular, brain, and lung cancer	Cytotoxic therapy, inducing apoptosis but not ICD unless combined with ER stress inducer		Martins et al. (2011)
Oxaliplatin	Colorectal cancer	Cytotoxic therapy, inducing ICD	Activation of the PERK-eIF2α pathway, resulting in CRT exposure	Tesniere et al. (2010) and Garg et al. (2012)
Mitoxantrone, idarubicin, epirubicin, and doxorubicin	Acute lymphoblastic leukemia, ovarian, and prostate cancer	Cytotoxic therapy, inducing ICD	Activation of the PERK-eIF2α pathway, resulting in CRT exposure	Fucikova et al. (2011) and Bezu et al. (2018)
Bleomycin	Testicular cancer and Hodgkin’s lymphoma	Cytotoxic therapy, inducing ICD and may also promoting Treg proliferation	Inducing ER stress through the generation of reactive oxygen species and exposing CRT though activation of the PERK-eIF2α pathway	Bugaut et al. (2013) and Garg et al. (2017)
Imatinib	Chronic myeloid leukemia, and gastric cancer	BCR-ABL tyrosine kinase inhibitor, promoting antitumor immune responses by inhibiting MDSCs and Treg function, while suppressing tumor immunity by inhibiting tumor antigens, DCs, and effector T cells	Inducing ER stress and resulting in apoptosis	Brauer et al. (2007), Larmonier et al. 2008), Heine et al. (2011), Hughes et al. (2017), and Kim et al. (2019)
Nilotinib and dasatinib	Chronic myeloid leukemia	BCR-ABL tyrosine kinase inhibitor, reducing MDSCs but not inducing ICD		Hughes et al. (2017)
Abemaciclib	Breast cancer	CDK4/6 inhibitor, enhancing tumor antigen presentation		Goel et al. (2017) and Schaer et al. (2018)
Palbociclib	Breast cancer	CDK4/6 inhibitor, activating effector T cells		Deng et al. (2018)
Gefitinib, erlontinib, afatinib, osimertinib, and olmutinib	NSCLC	EGFR inhibitors, decreasing PD-L1 expression and reducing Tregs		Yamaoka et al. (2017) and Li et al. (2018)
Cetuximab	Colorectal cancer	mAb competitively inhibiting EGFR, inducing ADCC and enhancing cross-presentation in DCs		Kimura et al. (2007), Srivastava et al. (2013), and Yamaoka et al. (2017)
Anti-GD2	Neuroblastoma	mAb targeting cell surface disialoganglioside GD2 and resulting in ADCC		Horta et al. (2016)
Ipilimumab	NSCLC and melanoma	mAb inhibiting CTLA-4		Pennock and Chow (2015) and Buchbinder and Desai (2016)
Nivolumab	NSCLC and melanoma	mAb inhibiting PD-1		Pennock and Chow (2015) and Buchbinder and Desai (2016)
Durvalumab	NSCLC	mAb targeting PD-L1		Antonia et al. (2017)
Metformin		Activating AMPK to phosphorylate PD-L1 and promote its degradation via ERAD	PD-L1 is degraded by ERAD but metformin does not target ERAD	Cha et al. (2018) and Dreher and Hoppe (2018)
Disulfram		Off-target effect on NPL4	Impairing ERAD by disrupting P97-NPL4-UFD1 complex and inhibiting proinflammatory macrophage responses	Skrott et al. (2017)