Emerging targets in cancer immunotherapy

Burugu, Samantha; Dancsok, Amanda R.; Nielsen, Torsten O.

doi:10.1016/j.semcancer.2017.10.001

Cited by 265 publications

(245 citation statements)

References 228 publications

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“…However, even among such potentially immunogenic cancers, immune checkpoint inhibitors benefit only a relatively small number of patients 7,12,14–18 . As resistance may be due to the activation of alternative checkpoint pathways, additional immune checkpoints targets have become a subject of active research, including the T-cell Immunoglobulin and Mucin-domain- containing molecule 3 (TIM-3) 19 .…”

Section: Introductionmentioning

confidence: 99%

TIM-3 expression in breast cancer

et al. 2018

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Tumor-infiltrating lymphocytes (TILs) are predominantly present in breast cancer patients with estrogen receptor negative tumors, among whom increasing levels correlate with favorable outcomes. Nevertheless, currently available immune checkpoint inhibitors appear to benefit only a small number of women with breast cancer. Upregulation of additional immune checkpoint markers is one mechanism of resistance to current inhibitors that might be amenable to targeting with newer agents. T-cell Immunoglobulin and Mucin domain-containing molecule 3 (TIM-3) is an immune checkpoint receptor that is an emerging target for cancer immunotherapy. We investigated TIM-3 immunohistochemical expression in 3,992 breast cancer specimens assembled into tissue microarrays, linked to detailed outcome, clinico-pathological parameters and biomarkers including CD8, PD-1, PD-L1 and LAG-3. We scored and reported absolute counts for TIM-3+ intra-epithelial and stromal TILs (iTILs and sTILs), and find that breast cancer patients with TIM-3+ iTILs (≥ 1) represent a minority of cases (11%), with a predilection for basal-like breast cancers (among which 28% had TIM-3+ iTILs). TIM-3+ sTILs (≥ 2) represented 20% of cases and included more non-basal cases. The presence of TIM-3+ iTILs highly correlates with hematoxylin and eosin-stained stromal TILs and with other immune checkpoint markers (PD-1+ iTILs, LAG-3+ iTILs and PD-L1+ tumors). In prognostic analyses, early breast cancer patients with TIM-3+ iTILs have significantly improved breast cancer-specific survival whereas TIM-3+ sTILs did not reach statistical significance. In multivariate analyses, the presence of TIM-3+ iTILs is an independent favorable prognostic factor in the whole cohort as well as among ER negative patients. Our study supports TIM-3 as a target for breast cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

TIM-3 expression in breast cancer

et al. 2018

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“…In addition to immune checkpoint inhibitors, 16 a second class of targeted immune-based therapy has been developed, chimeric antigen receptor T-cell therapy, which engineers the patient’s own T cells to recognize antigens on tumor cells. 17 Patients receiving this class of therapy also present with immune-related adverse events, and although the immune-related adverse events associated with chimeric antigen receptor T-cell therapy can be catastrophic (eg, encephalopathy, coma, fulminant hemophagocytic lymphohistiocytosis) and tend to occur closer to treatment initiation, similar considerations and recommendations apply.…”

Section: A New Age Of Cancer Treatment: Implications For Emergency Carementioning

confidence: 99%

Addressing New Diagnostic and Treatment Challenges Associated With a New Age of Cancer Treatment

Bischof

Presley

Caterino

2019

Annals of Emergency Medicine

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“…Along with surgery, radiotherapy, chemotherapy, and targeted therapy, immunotherapy is emerging as a new pillar of current cancer treatment . Targeting key immune checkpoints to restore the antitumor activity of T lymphocytes has been proved to be a safe and effective strategy for patients with advanced or metastatic malignancies in several international randomized controlled trials (RCTs) .…”

Section: Introductionmentioning

confidence: 99%