Tumor infiltrating lymphocytes (TILs)


Tumor infiltrating lymphocyte levels are markers of active antitumor immune response.

Tumor-infiltrating lymphocytes have left the bloodstream and migrated towards a tumor. 

Adoptive cell therapy with tumor infiltrating lymphocytes (TILs) is an autologous treatment that involves the ex vivo outgrowth and expansion of tumor resident T cells and subsequent intravenous adaptive transfer of the cells after preparation lympho depleting chemotherapy, supported by administration of interleukin-2 to enhance the in vivo expansion of the cells and augment tumor antitumor responses.

Tumor-infiltrating lymphocytes include T cells and B cells and and other tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells; T cells, B cells, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, eosinophils, and basophils.

While immunotherapy has transformed the management of advanced cancers, many patients do not receive long lasting clinical benefits from these agents.

T cells are the primary mediators of antitumor immunity and have a central role in the response to immunotherapies.

TIL abundance varies with tumor type and stage and in some cases relates to disease prognosis.


Immune effector cells such as CTL’s and NK cells with the help of dendritic and CD4+ T-cells are able to recognize and eliminate tumor cells.


TILs can often be found in the tumor stroma and within the tumor itself. 


TIL functions can dynamically change throughout tumor progression and in response to anticancer therapy.


TILs are implicated in killing tumor cells, and their presence in tumors is often associated with better clinical outcomes.


TILs can be found in between the tumor cells.


TILs in the stroma surrounding the tumor cells do not count.


CD3 is used to identify  lymphocytes in tumor samples, and tumor immune infiltration can also be determined by Microarray or RNA Sequencing.


An active immune environment within the tumor often indicates a better prognosis.


TILs as an adoptive cell transfer therapy can treat cancer especially melanoma.


TIL therapy can induce complete and durable regression of metastatic melanoma.

In patients with advanced melanoma progression free survival was significantly longer among those who received TIL (tumor infiltrating lymphocyte) therapy than among those who received ipilimumab.

Tumor reduction of 50% or more was observed in about half of patients, with  some patients experiencing complete responses with no detectable tumor remaining years after treatment.


TILs are associated with most effective immune checkpoint inhibitor therapy in GI cancers.


TILs are an important prognostic factor in melanoma and higher levels being associated with a better outcome.


TILs are also associated with better outcomes in epithelial ovarian cancer.


TILs prognostic value has been noted in colon cancer, bladder/urothelial cancers, oropharyngeal cancer, thyroid cancer, breast cancer, melanoma, and Merkel cell tumor.


TIL therapy in combination with immunotherapy treatment, associated with higher response rates and more durable responses in clinical trials. 

Tumor immune microenvironment plays an important role in prognosis in response to neoadjuvant chemotherapy in triple negative breast cancer.

Triple negative and HER2 positive breast cancers are known to have higher TIL amounts, and have been associated with improved prognosis and response to chemotherapy, which can help predict response to neoadjuvant treatment.

There are racial/ethnic differences in TILs in breast cancer patients: Native Hawaiian/Pacific Islanders, and Asian patients have increased TILs compared to White patients.

Stromal and intratumoral lymphocytes are reproducible markers confirming prognosis value in TNBC.

In triple negative breast cancer tumor infiltrating lymphocytes is associated with a favorable prognosis.

TNBCs are more likely than other types of breast cancers to be infiltrated with immune cells, in particular T cells.

In triple negative breast cancer, higher levels of TIL are associated with improved survival even without adjuvant or neoadjuvant therapy.

TNBCs are more likely to be positive for a programed death ligand 1 (PD-L 1).

TNBCs has a greater number of non-synonymous mutations, which give rise to tumor specific neoantigens they can activate neoantigen specific T cells to mount antitumor immune response, which can be strengthened by immune checkpoint inhibitors.

To receive TIL therapy, patient must have a good performance status an adequate organ and system function.

Older, frail patients, and those with severe organ dysfunction do not qualify.

TIL therapy is associated with the transient and manageable toxic affects related to the use of chemotherapy and intravenous IL-2.

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