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Tumor Discovery Fact & challenges of immunotherapy in TNBC

was two among 32 treated TNBC patients (range, 0 – 9). percentage of CD4 and CD8 T cells expressing inducible
+
+
Of these, 27 patients had their clinical responses evaluated. T-cell costimulator (ICOS) increased in all patients .
[73]
With 1 complete response (CR) and 4 PRs, the ORR was
18.5% (95% CI, 6.3 – 38.1%), and the DCR was 25.9% (95% 2.4.3. Neoadjuvant ipilimumab
CI, 11.1 – 46.3%) . These groundbreaking studies offer solid proof in favor of
[62]
By preventing the interaction of PD-L1 with PD-1 using PD-1/PD-L1 and CTLA-4 inhibitors in both early
and CD80 receptors (B7-1Rs), atezolizumab can be used and advanced TNBC. The FDA has authorized the use of
to treat dysplastic carcinoma, hepatocellular carcinoma pembrolizumab in conjunction with chemotherapy for
(HCC), non-small-cell lung cancer (NSCLC), small-cell the treatment of PD-L1-positive advanced TNBC, and
health authorities now recommend the combination of
lung cancer (SCLC), and TNBC [63,64] . Atezolizumab is a atezolizumab and nab-paclitaxel . To further understand
[55]
monoclonal antibody of the IgG1 isotype that has been the immunobiology of both early and late TNBC, well-
fully humanized and engineered to target the protein controlled translational studies may be conducted using
PD-L1 [13,65-67] . In the PCD4989g trial, atezolizumab was the data sets and tissue samples from these trials [49,60] .
tested in patients with advanced malignancies , including By identifying TNBC as a tumor that can react to
[68]
116 patients with advanced TNBC, 115 of whom had an immunotherapy, these studies collectively pave the way
objective response assessed. After the enrollment of the for the testing of cutting-edge ideas that can successfully
initial 25 patients, the eligibility was changed to permit harness the immune system to improve clinical outcomes
the enrollment of patients with any PD-Ll status. These for patients with this arduous condition (Table 3).
patients displayed PD-LI in IC, occupying <5% of the
tumor area. With 58% of patients having received at least 3. Challenges of immunotherapy in triple-
two prior lines of therapy for an incurable illness, the negative breast cancer
enrolled patients were severely treated [68,69] .
3.1. Unclear mechanism of tumor-infiltrating
2.4.2. Cytotoxic T-lymphocyte-associated protein 4 lymphocytes
inhibitors It is essential to consider whether the number of TILs
Ipilimumab is a monoclonal antibody that works to expressed in the primary tumor and the metastatic sites
activate the immune system by targeting CTLA-4, a protein can affect the prognosis of patients with TNBC. Another
receptor that downregulates the immune system. It boosts issue is whether the heterogeneity of TILs at the original
the immune response against cancer cells and prevents sites, the occurrence of residual invasive disease (RD)
the inhibitory interruption of cytotoxic T-lymphocytes following the completion of neoadjuvant chemotherapy
(CTLs), which can recognize and destroy cancer cells . In (NAC), and the metastatic locations can influence the
[70]
a study on early-stage BC, 12 of 18 women received a single choice of follow-up therapy options in TNBC [2,54] . Despite
dose of neoadjuvant ipilimumab alone or with additional the fact that the discovery of biomarkers has given
cryoablation; the other six patients received cryoablation individuals who are looking to advance their skills an
alone. T-cell density was found to be significantly effective tool, one of the main limitations of the use of TILs
correlated with TIL count by hematoxylin and eosin at the moment is their reliance on manual measurement,
[41]
(H&E). It was shown that about 5/6 patients who received which is subject to potential human error . Surprisingly,
ipilimumab alone had increased T-cell density in contrast there are many opportunities to employ computational
to the decrease in the cryoablation group [71,72] . techniques that extract spatial-morphologic predictive
elements, thus making it possible for computer-aided
Tremelimumab blocks the binding of antigen- diagnostics.
presenting cell ligands B7.1 and B7.2 to CTLA-4, resulting
in the inhibition of B7-CTLA-4-mediated downregulation We, now, need to figure out how to assess TILs in
of T-cell activation. Tremelimumab has been evaluated in combination with other biomarkers to direct a more
various types of tumors. Experiments with tremelimumab focused course of treatment, as they have been established
in combination with exemestane have been carried as distinct biomarkers in the early TNBC. In addition, it
out. Among 26 patients who received tremelimumab is still worthwhile to advocate the current belief that TILs
(3 – 10 mg/kg) and exemestane (25 mg/kg daily), five serve as the starting point for the expression of additional
[16,51]
patients developed dose-limiting toxicity when the dose biomarkers .
of tremelimumab with 25 mg/day exemestane was about In terms of immunomodulatory mechanisms, whether
6 mg/kg Q90D, four of which were diarrhea. Up to 42% negative immunomodulatory regulation, as part of a
of patients had stable disease for at least 12 weeks. The standard feedback loop, has a positive and persistent

Volume 1 Issue 2 (2022) 5 https://doi.org/10.36922/td.v1i2.196