Publicação
Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor
| Resumo: | Background: Studies pointed out that the tumor-infiltrating lymphocytes (TILs) have considerable importance in canine mammary tumor (CMT). On the other hand, cancer cells sometimes find ways to use immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system as programmed death 1 ligand 1 (PD-L1). In this study, it was investigated the relationship between PD-L1 expression, stromal tumor-infiltrating lymphocytes (TILs) in canine mammary tumor (CMT), and the association with clinical and pathological characteristics of the tumors. Materials, Methods & Results: PD-L1 expression and TILs were assessed in 23 female dogs with CMT. The tumors were grouped into simple carcinoma (CA, n = 8) and complex carcinoma (CC, n = 15). Stromal TILs were assessed using two thresholds as TILs-Low representing < 50% of infiltrate within stromal area and TILs-High representing = 50% of stromal area. Clinicopathological data of CMT was characterized according to key parameters, as well as survival rates. TILs evaluation within tumor stroma revealed that 65.2% (n = 15) of tumors had TILs-Low. PD-L1 expression and stromal TILs were significantly associated (P = 0.009). PD-L1 expression was observed in 39% (n = 9) of all tumors of which 17.4% (n = 4) were from CA group and 21.7% (n = 5) were from CC group. PD-L1 expression within TILs was observed in 39% (n = 9) of the tumors. PD-L1 in malignant epithelium was present in all lymph node metastasis (n = 5). PD-L1 was associated with involvement of regional lymph nodes (P = 0.034). Survival curves demonstrated TILs-Low had higher (P = 0.010) overall survival (OS) compared with TILs-High, and PD-L1+ and PD-L1– (P = 0.06) did not differed. The clinicopathological variables significantly correlated with OS by univariate analysis were the histological grade (P = 0.009), lymph node involvement (P = 0.004), stromal TILs (P = 0.016), and PD-L1+/TILs-High vs. PD-L1–/TILs-Low (P = 0.010). Multivariate analysis revealed that group of tumors with grade II-III was independent and negative prognostic factors for OS. Discussion: In this study, PD-L1 was differently expressed according to the histologic subtypes of TMC. Currently, has been showed the presence of PD-L1 in several canine cancer. Nevertheless, only a few studies have described PD-L1 protein expression in dog tumors and showed PD-L1 was constitutively expressed on canine tumor cell lines, although the levels of basal expression were very variable. This expression can be modulated by IFN-¿ exposure. In the present study, it was found a strong PD-L1 expression on TILs. The increase in PD-L1 cell surface expression by tumor cells can lead to decreased T-cell proliferation and increased apoptosis. In human breast cancer (BC) the PD-L1 expression was expressed in TILs and tumor epithelium. It has been reported the association of stromal TILs and PD-L1 expression with aggressive types and stages of BC. In this study, it was detected PD-L1 expression in malignant epithelium in all lymph node metastasis. PD-L1 overexpression was significantly associated with a series of clinicopathological parameters. It was demonstrated that PD-L1+/TILs-High had higher risk of overall survival (OS) than another group of interaction. High PDL1 expression may be a prognostic indicator for reduced OS, while tumor PD-L1+ was associated with poorer disease-free survival. The presence of TILs has shown to be potentially predictive and a prognostic factor in BC subtypes. In CMT, it has been reported that a high proportion of TILs was correlated to several malignancy characteristics. In relation to PDL1, further research is necessary to clarify this immune checkpoint as a potential therapeutic target and its application in clinical practice in CMT. |
|---|---|
| Autores principais: | Lopes-Neto, BE |
| Outros Autores: | Nunes-Pinheiro, DCS; Carvalheira, JGV; Schmitt, F; Gärtner, F |
| Assunto: | Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Porto |
| Idioma: | inglês |
| Origem: | Repositório Aberto da Universidade do Porto |
| _version_ | 1867767322532380672 |
|---|---|
| author | Lopes-Neto, BE |
| author2 | Nunes-Pinheiro, DCS Carvalheira, JGV Schmitt, F Gärtner, F |
| author2_role | author author author author |
| author_facet | Lopes-Neto, BE Nunes-Pinheiro, DCS Carvalheira, JGV Schmitt, F Gärtner, F |
| author_role | author |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Lopes-Neto, BE\"},{\"Person.name\":\"Nunes-Pinheiro, DCS\"},{\"Person.name\":\"Carvalheira, JGV\"},{\"Person.name\":\"Schmitt, F\"},{\"Person.name\":\"Gärtner, F\"}] |
| datacite.creators.creator.creatorName.fl_str_mv | Lopes-Neto, BE Nunes-Pinheiro, DCS Carvalheira, JGV Schmitt, F Gärtner, F |
| datacite.date.Accepted.fl_str_mv | 2021-01-01T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| datacite.titles.title.fl_str_mv | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| dc.creator.none.fl_str_mv | Lopes-Neto, BE Nunes-Pinheiro, DCS Carvalheira, JGV Schmitt, F Gärtner, F |
| dc.date.Accepted.fl_str_mv | 2021-01-01T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/10216/152467 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | UNIV FED RIO GRANDE DO SUL |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| dc.title.fl_str_mv | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Background: Studies pointed out that the tumor-infiltrating lymphocytes (TILs) have considerable importance in canine mammary tumor (CMT). On the other hand, cancer cells sometimes find ways to use immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system as programmed death 1 ligand 1 (PD-L1). In this study, it was investigated the relationship between PD-L1 expression, stromal tumor-infiltrating lymphocytes (TILs) in canine mammary tumor (CMT), and the association with clinical and pathological characteristics of the tumors. Materials, Methods & Results: PD-L1 expression and TILs were assessed in 23 female dogs with CMT. The tumors were grouped into simple carcinoma (CA, n = 8) and complex carcinoma (CC, n = 15). Stromal TILs were assessed using two thresholds as TILs-Low representing < 50% of infiltrate within stromal area and TILs-High representing = 50% of stromal area. Clinicopathological data of CMT was characterized according to key parameters, as well as survival rates. TILs evaluation within tumor stroma revealed that 65.2% (n = 15) of tumors had TILs-Low. PD-L1 expression and stromal TILs were significantly associated (P = 0.009). PD-L1 expression was observed in 39% (n = 9) of all tumors of which 17.4% (n = 4) were from CA group and 21.7% (n = 5) were from CC group. PD-L1 expression within TILs was observed in 39% (n = 9) of the tumors. PD-L1 in malignant epithelium was present in all lymph node metastasis (n = 5). PD-L1 was associated with involvement of regional lymph nodes (P = 0.034). Survival curves demonstrated TILs-Low had higher (P = 0.010) overall survival (OS) compared with TILs-High, and PD-L1+ and PD-L1– (P = 0.06) did not differed. The clinicopathological variables significantly correlated with OS by univariate analysis were the histological grade (P = 0.009), lymph node involvement (P = 0.004), stromal TILs (P = 0.016), and PD-L1+/TILs-High vs. PD-L1–/TILs-Low (P = 0.010). Multivariate analysis revealed that group of tumors with grade II-III was independent and negative prognostic factors for OS. Discussion: In this study, PD-L1 was differently expressed according to the histologic subtypes of TMC. Currently, has been showed the presence of PD-L1 in several canine cancer. Nevertheless, only a few studies have described PD-L1 protein expression in dog tumors and showed PD-L1 was constitutively expressed on canine tumor cell lines, although the levels of basal expression were very variable. This expression can be modulated by IFN-¿ exposure. In the present study, it was found a strong PD-L1 expression on TILs. The increase in PD-L1 cell surface expression by tumor cells can lead to decreased T-cell proliferation and increased apoptosis. In human breast cancer (BC) the PD-L1 expression was expressed in TILs and tumor epithelium. It has been reported the association of stromal TILs and PD-L1 expression with aggressive types and stages of BC. In this study, it was detected PD-L1 expression in malignant epithelium in all lymph node metastasis. PD-L1 overexpression was significantly associated with a series of clinicopathological parameters. It was demonstrated that PD-L1+/TILs-High had higher risk of overall survival (OS) than another group of interaction. High PDL1 expression may be a prognostic indicator for reduced OS, while tumor PD-L1+ was associated with poorer disease-free survival. The presence of TILs has shown to be potentially predictive and a prognostic factor in BC subtypes. In CMT, it has been reported that a high proportion of TILs was correlated to several malignancy characteristics. In relation to PDL1, further research is necessary to clarify this immune checkpoint as a potential therapeutic target and its application in clinical practice in CMT. |
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| identifier.url.fl_str_mv | https://hdl.handle.net/10216/152467 |
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| institution | Universidade do Porto |
| instname_str | Universidade do Porto |
| language | eng |
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| organization_str_mv | urn:organizationAcronym:up |
| person_str_mv | Lopes-Neto, BE Nunes-Pinheiro, DCS Carvalheira, JGV Schmitt, F Gärtner, F |
| publishDate | 2021 |
| publisher.none.fl_str_mv | UNIV FED RIO GRANDE DO SUL |
| reponame_str | Repositório Aberto da Universidade do Porto |
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| spelling | Background: Studies pointed out that the tumor-infiltrating lymphocytes (TILs) have considerable importance in canine mammary tumor (CMT). On the other hand, cancer cells sometimes find ways to use immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system as programmed death 1 ligand 1 (PD-L1). In this study, it was investigated the relationship between PD-L1 expression, stromal tumor-infiltrating lymphocytes (TILs) in canine mammary tumor (CMT), and the association with clinical and pathological characteristics of the tumors. Materials, Methods & Results: PD-L1 expression and TILs were assessed in 23 female dogs with CMT. The tumors were grouped into simple carcinoma (CA, n = 8) and complex carcinoma (CC, n = 15). Stromal TILs were assessed using two thresholds as TILs-Low representing < 50% of infiltrate within stromal area and TILs-High representing = 50% of stromal area. Clinicopathological data of CMT was characterized according to key parameters, as well as survival rates. TILs evaluation within tumor stroma revealed that 65.2% (n = 15) of tumors had TILs-Low. PD-L1 expression and stromal TILs were significantly associated (P = 0.009). PD-L1 expression was observed in 39% (n = 9) of all tumors of which 17.4% (n = 4) were from CA group and 21.7% (n = 5) were from CC group. PD-L1 expression within TILs was observed in 39% (n = 9) of the tumors. PD-L1 in malignant epithelium was present in all lymph node metastasis (n = 5). PD-L1 was associated with involvement of regional lymph nodes (P = 0.034). Survival curves demonstrated TILs-Low had higher (P = 0.010) overall survival (OS) compared with TILs-High, and PD-L1+ and PD-L1– (P = 0.06) did not differed. The clinicopathological variables significantly correlated with OS by univariate analysis were the histological grade (P = 0.009), lymph node involvement (P = 0.004), stromal TILs (P = 0.016), and PD-L1+/TILs-High vs. PD-L1–/TILs-Low (P = 0.010). Multivariate analysis revealed that group of tumors with grade II-III was independent and negative prognostic factors for OS. Discussion: In this study, PD-L1 was differently expressed according to the histologic subtypes of TMC. Currently, has been showed the presence of PD-L1 in several canine cancer. Nevertheless, only a few studies have described PD-L1 protein expression in dog tumors and showed PD-L1 was constitutively expressed on canine tumor cell lines, although the levels of basal expression were very variable. This expression can be modulated by IFN-¿ exposure. In the present study, it was found a strong PD-L1 expression on TILs. The increase in PD-L1 cell surface expression by tumor cells can lead to decreased T-cell proliferation and increased apoptosis. In human breast cancer (BC) the PD-L1 expression was expressed in TILs and tumor epithelium. It has been reported the association of stromal TILs and PD-L1 expression with aggressive types and stages of BC. In this study, it was detected PD-L1 expression in malignant epithelium in all lymph node metastasis. PD-L1 overexpression was significantly associated with a series of clinicopathological parameters. It was demonstrated that PD-L1+/TILs-High had higher risk of overall survival (OS) than another group of interaction. High PDL1 expression may be a prognostic indicator for reduced OS, while tumor PD-L1+ was associated with poorer disease-free survival. The presence of TILs has shown to be potentially predictive and a prognostic factor in BC subtypes. In CMT, it has been reported that a high proportion of TILs was correlated to several malignancy characteristics. In relation to PDL1, further research is necessary to clarify this immune checkpoint as a potential therapeutic target and its application in clinical practice in CMT.application/pdfengUNIV FED RIO GRANDE DO SULRelationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumorLopes-Neto, BENunes-Pinheiro, DCSCarvalheira, JGVSchmitt, FGärtner, FHandlehttps://hdl.handle.net/10216/152467ISSNIsPartOf1678-0345DOIIsPartOf10.22456/1679-9216.10260020212021-01-01T00:00:00Zhttp://purl.org/coar/access_right/c_abf2open accessBreast cancerCanine mammary tumorsImmune checkpointOverall survivalPD-L1Prognosis1109517 byteshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio-aberto.up.pt/bitstream/10216/152467/1/10.22456-1679-9216.102600.pdfliteraturehttp://purl.org/coar/resource_type/c_6501journal article |
| spellingShingle | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor Lopes-Neto, BE Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| status | SINGLETON |
| subject.fl_str_mv | Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| title | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| title_full | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| title_fullStr | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| title_full_unstemmed | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| title_short | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| title_sort | Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor |
| topic | Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| topic_facet | Breast cancer Canine mammary tumors Immune checkpoint Overall survival PD-L1 Prognosis |
| url | https://hdl.handle.net/10216/152467 |
| visible | 1 |