Tumor immunology

Sharif, Pouya Mahdavi; Khoshbin, Amin Pastaki; Nasrollahzadeh, Elaheh; Keshavarz-Fathi, Mahsa; Rezaei, Nima

doi:10.1016/b978-0-12-818006-8.00003-7

Cited by 3 publications

(3 citation statements)

References 1,098 publications

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“…Immune checkpoint inhibitors are now a part of standard anti-neoplastic regimens in a relatively wide range of cancers, including melanoma, non-small cell lung cancer, renal cell carcinoma, endometrial carcinoma, colorectal cancer, etc. [ 8 ]. However, as mentioned, response to this class of drugs is generally short-lived [ 8 ], the anti-drug resistance appears in a relatively short-term period [ 19 ], and their side effects are noticeable, and lethal in some instances [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…[ 8 ]. However, as mentioned, response to this class of drugs is generally short-lived [ 8 ], the anti-drug resistance appears in a relatively short-term period [ 19 ], and their side effects are noticeable, and lethal in some instances [ 20 ]. As a result, it is prudent to meticulously select candidates who benefit most from these agents and to wield the potential of simultaneous blockade of more than one immunomodulator.…”

Section: Discussionmentioning

confidence: 99%

“…Despite unprecedented outcomes of immunotherapies with immune checkpoint inhibitors (ICIs) for a wide range of malignancies, the landscape of ICI monotherapy has not been promising for breast cancers [ 8 ]. Moreover, the short-term efficacy of these therapies, even those with a promising initial response, and the limited number of eligible cases for these agents, combination therapies with ICIs, cancer vaccines, chemotherapeutic agents, or radiation therapies have been persuaded [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of immune checkpoints expression and lymphocyte densities of iranian breast cancer patients; the co-expression status and clinicopathological associates

et al. 2023

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Background Breast malignancies are now the most common and deadliest type of neoplasms among women worldwide. Novel therapeutic approaches are needed to combat advanced stages of breast cancer. In this study, we aimed to investigate the expression and co-expression status of three immune checkpoints (PD-1, PD-L1, and LAG-3), as well as tumor-infiltrating lymphocytes (TIL) scores, and to further establish their potential correlations with clinicopathologic features. Methods We performed a retrospective study on 361 pathologic samples of breast cancer. Immunohistochemistry was performed to assess the status of the immune checkpoint markers, and H&E staining was used to score TILs. The correlations of the immune checkpoint markers of tumor cells and tumor-associated immune cells and TIL scores with clinicopathological characteristics were analyzed. Results Out of 361 assessed samples, LAG-3 was positive in 51%, while IC PD-L1 and TC PD-L1 were detectable in 36% and 8.9%, respectively. Moreover, both IC PD-L1 and LAG-3 stained positively in 24.4% of samples. IC PD-L1 expression was significantly higher in tumors with higher nuclear, mitotic, and overall grades and tubule formation. In addition, TC PD-L1 and LAG-3 exhibited a similar trend for higher overall grading. Tumors with positive estrogen- and progesterone-receptor (ER and PR) expression had significantly lower IC PD-L1 and TC PD-L1 staining, while LAG-3 positivity was more prevalent in HER2 positive samples. Tumors that were positive for these biomarkers had significantly higher Ki-67 scores. LAG-3 expression showed significant correlations with PD-1 and IC PD-L1 expression. Besides, the co-expression of LAG-3 and IC PD-L1 was significantly more encountered in luminal B and triple-negative subtypes, compared to the luminal A subtype. Regarding TILs, their scoring was significantly higher in ER and PR negative and HER2 positive samples. Intriguingly, samples with positive staining for LAG-3, IC PD-L1, and TC PD-L1 had significantly higher TIL scorings. Conclusions Immune checkpoints show differentially different levels of expression in certain molecular subtypes of breast cancer. Moreover, they reveal a meaningful correlation with each other, proliferation indices, and histologic grades. Finally, a sizable proportion of breast cancers co-express PD-L1 and LAG-3, which will make them appropriate targets for future combined ICIs.

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