Table Info

Table 1.

Immunotherapeutic agents and their immune response in different subtypes of breast cancer

Sl. No.	Immunotherapy	Immunotherapy agent	Breast cancer subtype	Immune response	References
1	CTLA-4 blockade in breast cancer	Tremelimumab	ER⁺/HER2^– breast cancer	Significant increase in the ratio of ICOS⁺/FoxP3⁺ and CD4⁺ T-cells was observed	[58]
2	CTLA-4 blockade in breast cancer	Ipilimumab	Early breast cancer prior to mastectomy; any HR, HER2, and nodal status were permitted	Immunotherapy with cryoablation induced circulating T helper type 1 cytokines, ICOS⁺ and Ki67⁺ CD4⁺ and CD8⁺ T-cells, and an increased CD8⁺ T-cell/FoxP3⁺ Treg ratio within the tumor	[59]
3	PD1/PDL1 blockade in breast cancer	Avelumab	TNBC	Blocking PDL1, T-cells function better and the immune response is stimulated to find and kill cancer cells	[60]
4	PD1/PDL1 blockade in breast cancer	Atezolizumab	TNBC	Blocking PDL-1, T-cells function better and the immune response is stimulated to find and kill cancer cells	[61]
5	PD1/PDL1 blockade in breast cancer	Pembrolizumab	Metastatic PDL1⁺ TNBC	Human monoclonal antibodies that inhibit the interaction between PD1 and PDL1. This prevents the downregulation of T-cells and tumor cell evasion of normal immune surveillance	[62]
6	HER2-directed immunotherapy	Herceptin (trastuzumab)	Early and late-stage HER2-overexpressing breast cancer	Trastuzumab-dependent NK activation leads to cytokine secretion contributing to the recruitment and functional polarization of myeloid and T-cells. Exert a vaccine-like effect activating the adaptive as well as the innate immune system	[63]
7	HER2-directed immunotherapy	Pertuzumab	Early and late-stage HER-2-overexpressing breast cancer	Directed against the extracellular dimerization domain of HER2 (a different epitope than trastuzumab). Its binding inhibits dimerization of HER2 with other receptors of the HER family; increases the density of FcγR binding sites on HER2⁺ cells, possibly enhancing NK-mediated ADCC responses	[64]
8	HER2-directed immunotherapy	Lapatinib	HER2⁺ breast cancer	Reversible inhibitor of both HER2 and EGFR intracellular tyrosine kinase domains; promotes tumor infiltration by CD4⁺, CD8⁺, IFN-γ-producing T-cells through a Stat1 dependent pathway	[65]
9	HER2-directed immunotherapy	T-DM1	HER2⁺ breast cancer	Antibody-drug conjugate formed by trastuzumab linked to the cytotoxic agent DM1. After binding HER2, T-DM1 is internalized, degraded in the endosome, releasing DM1. In addition, T-DM1 blocks HER2 signaling pathway and mediates ADCC	[66]
10	HER2-directed immunotherapy	Neratinib	HER2⁺ breast cancer	It is a pan-HER tyrosine kinase inhibitor. It bonds covalently to a conserved cysteine residue, leading to irreversible inhibition of all four HER receptors, block of downstream pathways, and in vitro inhibition of proliferation in tumor cells with trastuzumab resistance	[67]

Sl. No.: serial number; ICOS: inducible costimulatory; HR: hormone receptor; ADCC: antibody-dependent cellular cytotoxicity; EGFR: epidermal growth factor receptor; DM1: emtansine; T-DM1: ado-trastuzumab DM1

Declarations

Acknowledgments

The authors acknowledge Amity University Utter Pradesh, Noida for providing the platform to continue with the research related to breast cancer immunobiology and the generation of ideas answering the present status of immune response in breast cancer. The authors acknowledge the ICMR-Indian Council of Medical Research for the opportunity to work in ICMR laboratories.

Author contributions

BB: Conceptualization, Investigation, Supervision, Writing—original draft, Writing—review & editing. SH: Writing—review & editing. VK: Writing—review & editing.

Conflicts of interest

The authors declare no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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