The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications
Tumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.628063/full |
| _version_ | 1828964504137891840 |
|---|---|
| author | Ahmet Murat Aydin Brittany L. Bunch Matthew Beatty Ali Hajiran Jasreman Dhillon Amod A. Sarnaik Amod A. Sarnaik Shari Pilon-Thomas Shari Pilon-Thomas Shari Pilon-Thomas Michael A. Poch |
| author_facet | Ahmet Murat Aydin Brittany L. Bunch Matthew Beatty Ali Hajiran Jasreman Dhillon Amod A. Sarnaik Amod A. Sarnaik Shari Pilon-Thomas Shari Pilon-Thomas Shari Pilon-Thomas Michael A. Poch |
| author_sort | Ahmet Murat Aydin |
| collection | DOAJ |
| description | Tumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have previously shown that expansion of tumor reactive TIL from primary bladder tumors and lymph node metastases is feasible. Here, we performed TIL harvesting from additional surgical specimens (additional 31 primary tumors and 10 lymph nodes) to generate a heterogenous cohort of 53 patients with bladder cancer (BC) to evaluate the tumor characteristics that lead to tumor-reactive TIL expansion. Among a total of 53 patients, overall TIL growth from tumor samples were 37/53 (69.8%) and overall anti-tumor reactive TIL were 26/35 (74.3%). Mixed urothelial carcinoma is associated with higher anti-tumor reactivity of expanded TIL than pure urothelial carcinoma (89.5% vs. 56.3%, p=0.049). The anti-tumor reactivity of expanded TIL from primary tumors previously treated with BCG immunotherapy were lower (33.3% vs. 82.6%, p=0.027) although T-cell phenotype (CD3+, CD4+, CD8+, and CD56+) was similar regardless prior of BCG therapy. Addition of agonistic 4-1BB antibody in culture media with IL-2 improved the number of expanded TIL from primary tumors previously treated with BCG immunotherapy. There was no significant difference between basal and luminal subtype tumors in terms of viable and reactive TIL growth. Our study demonstrates that TIL expansion is feasible across all BC patients and BC subtypes, and we suggest that TIL therapy can be a reasonable treatment strategy for various manifestations of BC. |
| first_indexed | 2024-12-14T10:50:27Z |
| format | Article |
| id | doaj.art-90a50ca283db47c89748bd948ad255ee |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T10:50:27Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-90a50ca283db47c89748bd948ad255ee2022-12-21T23:05:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.628063628063The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic ApplicationsAhmet Murat Aydin0Brittany L. Bunch1Matthew Beatty2Ali Hajiran3Jasreman Dhillon4Amod A. Sarnaik5Amod A. Sarnaik6Shari Pilon-Thomas7Shari Pilon-Thomas8Shari Pilon-Thomas9Michael A. Poch10Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Immunology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Immunology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Pathology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Immunology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Immunology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, United StatesDepartment of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, United StatesTumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have previously shown that expansion of tumor reactive TIL from primary bladder tumors and lymph node metastases is feasible. Here, we performed TIL harvesting from additional surgical specimens (additional 31 primary tumors and 10 lymph nodes) to generate a heterogenous cohort of 53 patients with bladder cancer (BC) to evaluate the tumor characteristics that lead to tumor-reactive TIL expansion. Among a total of 53 patients, overall TIL growth from tumor samples were 37/53 (69.8%) and overall anti-tumor reactive TIL were 26/35 (74.3%). Mixed urothelial carcinoma is associated with higher anti-tumor reactivity of expanded TIL than pure urothelial carcinoma (89.5% vs. 56.3%, p=0.049). The anti-tumor reactivity of expanded TIL from primary tumors previously treated with BCG immunotherapy were lower (33.3% vs. 82.6%, p=0.027) although T-cell phenotype (CD3+, CD4+, CD8+, and CD56+) was similar regardless prior of BCG therapy. Addition of agonistic 4-1BB antibody in culture media with IL-2 improved the number of expanded TIL from primary tumors previously treated with BCG immunotherapy. There was no significant difference between basal and luminal subtype tumors in terms of viable and reactive TIL growth. Our study demonstrates that TIL expansion is feasible across all BC patients and BC subtypes, and we suggest that TIL therapy can be a reasonable treatment strategy for various manifestations of BC.https://www.frontiersin.org/articles/10.3389/fimmu.2021.628063/fulladoptive cellular immunotherapyBacillus Calmette–Guerinmolecular subtypesbladder cancertumor-infiltrating lymphocytes |
| spellingShingle | Ahmet Murat Aydin Brittany L. Bunch Matthew Beatty Ali Hajiran Jasreman Dhillon Amod A. Sarnaik Amod A. Sarnaik Shari Pilon-Thomas Shari Pilon-Thomas Shari Pilon-Thomas Michael A. Poch The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications Frontiers in Immunology adoptive cellular immunotherapy Bacillus Calmette–Guerin molecular subtypes bladder cancer tumor-infiltrating lymphocytes |
| title | The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications |
| title_full | The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications |
| title_fullStr | The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications |
| title_full_unstemmed | The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications |
| title_short | The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications |
| title_sort | factors affecting expansion of reactive tumor infiltrating lymphocytes til from bladder cancer and potential therapeutic applications |
| topic | adoptive cellular immunotherapy Bacillus Calmette–Guerin molecular subtypes bladder cancer tumor-infiltrating lymphocytes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.628063/full |
| work_keys_str_mv | AT ahmetmurataydin thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT brittanylbunch thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT matthewbeatty thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT alihajiran thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT jasremandhillon thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT amodasarnaik thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT amodasarnaik thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT sharipilonthomas thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT sharipilonthomas thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT sharipilonthomas thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT michaelapoch thefactorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT ahmetmurataydin factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT brittanylbunch factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT matthewbeatty factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT alihajiran factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT jasremandhillon factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT amodasarnaik factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT amodasarnaik factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT sharipilonthomas factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT sharipilonthomas factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT sharipilonthomas factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications AT michaelapoch factorsaffectingexpansionofreactivetumorinfiltratinglymphocytestilfrombladdercancerandpotentialtherapeuticapplications |