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Tumor Discovery Fact & challenges of immunotherapy in TNBC

density, the higher the risk of BC . Breast tissue density 5 – 26%) of breast cancers are lymphocyte-predominant
[37]
screening could be a promising and quick approach for breast cancers (LPBCs), among which TNBC accounts for
rational surveillance. According to several epidemiological the highest incidence (20%; range, 4 – 37%) . Moreover,
[50]
studies, obesity is a potential risk factor for BC [38,39] . Hence, CD8 T-cell infiltrates have been observed in 60% of TNBC
+
[41]
engaging in physical activity is considered the best way cases . Various tests that employ different antibodies
to prevent BC. Alcohol and alcoholic beverages can also and scoring methods are commercially available. There is
increase the risk of malignancy . an ongoing debate over the optimal assay for TNBC and
[40]
whether the findings hold for all ICIs.
2.2. Triple-negative breast cancer microenvironment
2.4. Drugs
The tumor microenvironment (TME) contains various cell
types, including fibroblasts, TILs, and lymphatic vascular ICIs, especially for CTLA-4, PD-L1, and PD-1, have made
channels. The active interaction between tumor cells great contributions to cancer therapy. The five drugs in
and the microenvironment affects the pathogenesis and TNBC immunotherapy include avelumab, pembrolizumab,
development of tumor. Research has indicated that high and atezolizumab, ipilimumab, and tremelimumab.
levels of TILs, especially in the IM subtype, are associated
with better prognosis and response to chemotherapy in 2.4.1. Programmed cell death 1/programmed cell
both neoadjuvant and adjuvant contexts [1,4] . Later, research death-ligand 1 inhibitors
has revealed that variations in gene overexpression Avelumab, a complete monoclonal antibody of the
of IM and MSL subtypes are derived from the TME, isotype IgG1 that binds to PD-L1 and prevents binding
including infiltrating immune cells and tumor-associated to its receptor PD-1, acts as a checkpoint inhibitor, and is
mesenchymal tissue, respectively [41,42] . Intriguingly, and in being utilized in the immunotherapy for various types of
agreement with the aforementioned findings, these genes advanced or metastatic cancers [51,52] . In the TNBC subgroup
are not expressed in cell lines when tests are conducted treated with avelumab, there were three partial responses
in vitro, where the microenvironment is absent. It is evident (PRs), giving TNBC patients an objective response rate
that TME has a significant influence on the development of (ORR) of 5.2% (95% CI, 1.1 – 14.4%). The disease control
tumor as well as the response and resistance to treatment. rates (DCRs) were 28% (47/168) and 31% (18/58) for the
Furthermore, the elevated expression of immune regulators overall population and the TNBC subgroup, respectively.
such as CTLA4, PD-1, and PD-L1 in TNBC, brought on Both the overall population and the TNBC subgroup
by lymphocyte infiltration of the tumor, is likely linked showed a tendency toward higher ORRs in patients
to a response to ICIs. Several studies have purported with PD-L1 expression in tumor-associated ICs (10%
the possibility that TILs may be a marker for improved cutoff), with ORRs of 16.7% (2/12 patients) and 22.2%
survival outcomes [43-45] . All the preceding evidence suggests (2/9), respectively, for PD-L1-positive disease and 1.6%
that focusing on TME in TNBC and further exploring (2/124 patients) and 2.6% (1/39 patients), respectively, for
[53]
the biomarker landscape are promising efforts for better PD-L1-negative disease .
immunotherapy. A humanized antibody, pembrolizumab, is used in
2.3. Specific biomarkers cancer immunotherapy to treat melanoma, lung, head
and neck, stomach, cervical, and breast cancers, as well
Due to the underlying heterogeneity of TNBC, there is as Hodgkin lymphoma. Pembrolizumab is slowly injected
a need for efficient biomarkers that can guide doctors in into a vein. The IgG4 isotype antibody blocks the defense
determining the best course of action. Therapeutic trials mechanism of cancer cells, thus enabling the immune
have been conducted on several suggested biomarkers system to eliminate them. Pembrolizumab targets the
for TNBC, with limited clinical benefits so far. Breast lymphocyte PD-1 receptor and functions by concentrating
cancer gene (BRCA1/BRCA2) mutations have been on the PD-1/PD-L1 biological pathway, which is present in
found to be predictive of the effectiveness of poly (ADP- some cancer cells and immune cells in the body [6,54-61] . The
ribose) polymerase (PARP) inhibitors, and changes to PD-1 antagonist pembrolizumab, in the KEYNOTE-012
other homologous recombination-related genes appear trial, which studied the safety and antitumor efficacy of
promising in this context [46-49] . It is possible to use the pembrolizumab monotherapy in patients with advanced
expression of PD-L1 protein in either immune cells (ICs) PD-L1-positive solid tumors, was initially assessed
or tumor cells, or both, as a biomarker to predict how well in PD-LI-positive advanced TNBC patients. PD-L1
an immune checkpoint inhibitor would work . TILs are expression was prescreened in 111 patients with advanced
[15]
also considered an important prognostic factor in TNBC. TNBC, in which 58.6% of them tested positive for PD-L1.
Up to 15 studies have shown that 11% (median; range, The median number of prior therapies for advanced illness

Volume 1 Issue 2 (2022) 4 https://doi.org/10.36922/td.v1i2.196