The failure of immune checkpoint blockade in multiple myeloma with pd-1 inhibitors in a phase 1 study

Access through your institution Buy or subscribe The failure of significant clinical responses to immune checkpoint blockade in multiple myeloma in comparison with other lymphoid

malignancies (especially Hodgkin’s lymphoma) raises considerable questions as to our understanding of human T-cell anti-tumour responses in myeloma. The report by Ray _et al._1 presented _in

vitro_ data, which suggested that the inhibition of PD-1/ PD-L1 ligation would be a potentially useful therapeutic modality in myeloma. Although this appears to be supported by preclinical

murine studies, this data is at variance to the observations being reported in clinical studies in myeloma.2 For immune checkpoint inhibition to be a successful modality, there must be

immune recognition of malignant myeloma cells and the presence of T cells that are capable of being activated. Such activation requires T cells to have an exhausted phenotype rather than an

anergic or senescent phenotype as it is the reversal of exhausted T cells rather than the generation of new T cells reacting to the tumour, which is thought to be the key to therapeutic

response. The possibility that cytotoxic T cells against common pathogens may be cross reacting with neoantigens from the tumour has been raised in melanoma,3 and it remains a possibility

that cytotoxic T cells can be activated by checkpoint blockade that cross react against myeloma. It has certainly been possible to educate and generate T cells from myeloma patients to

malignant plasma cell lines and tumour lysates _in vitro_, but whether such _in vitro_ recognition and activation reflects the situation _in vivo_ is unclear. The non-clonal T cells

(CD8+TCRVβ−CD57+) in myeloma are unlikely to be tumour reactive but the specific phenotype of the clonal T cells (CD8+TCRVβ+CD57+CD28−) suggest antigen specific, terminally differentiated,

senescent cells that have lost their ability to proliferate under stimulation. Studies that use pooled cytotoxic CD8+ T cells will contain both clonal and non-clonal T cells and therefore

may not be of clinical significance. This is a preview of subscription content, access via your institution RELEVANT ARTICLES Open Access articles citing this article. * ONCOLYTIC MEASLES

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April 2020 * DEVELOPMENT OF A PROTEIN-BASED SYSTEM FOR TRANSIENT EPIGENETIC REPRESSION OF IMMUNE CHECKPOINT MOLECULE AND ENHANCEMENT OF ANTITUMOUR ACTIVITY OF NATURAL KILLER CELLS * Yoichi

Teratake * , Tomoki Takashina *  … Yukihito Ishizaka _British Journal of Cancer_ Open Access 21 January 2020 * CARFILZOMIB ALTERS THE HLA-PRESENTED PEPTIDOME OF MYELOMA CELLS AND IMPAIRS

PRESENTATION OF PEPTIDES WITH AROMATIC C-TERMINI * D J Kowalewski * , S Walz *  … J S Stickel _Blood Cancer Journal_ Open Access 08 April 2016 ACCESS OPTIONS Access through your institution

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Contact customer support REFERENCES * Ray A, Das DS, Song Y, Richardson P, Munshi NC, Chauhan D _et al_. Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cells interactions

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a replicative history that is distinct from their CD28+CD8+ counterparts. _J Immunol_ 1996; 156: 3587–3590. CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Institute of Haematology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia H Suen, R Brown, S Yang, P J Ho, J Gibson & D Joshua Authors * H Suen View

author publications You can also search for this author inPubMed Google Scholar * R Brown View author publications You can also search for this author inPubMed Google Scholar * S Yang View

author publications You can also search for this author inPubMed Google Scholar * P J Ho View author publications You can also search for this author inPubMed Google Scholar * J Gibson View

author publications You can also search for this author inPubMed Google Scholar * D Joshua View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to H Suen. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Suen, H., Brown, R., Yang, S. _et al._ The failure of immune checkpoint blockade in multiple myeloma with PD-1 inhibitors in a phase 1 study. _Leukemia_ 29, 1621–1622 (2015).

https://doi.org/10.1038/leu.2015.104 Download citation * Published: 19 May 2015 * Issue Date: July 2015 * DOI: https://doi.org/10.1038/leu.2015.104 SHARE THIS ARTICLE Anyone you share the

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