A Journey in Science: Immersion in the search for effective cancer immunotherapies

Rosenberg, Steven A.

doi:10.1186/s10020-021-00321-3

Cited by 10 publications

(8 citation statements)

References 88 publications

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“…After Dr Rosenberg discovered that TILs can be cultured with the aid of the cytokine interleukin (IL)-2 and induced TILexhibited cytotoxic activity against melanoma cells in vitro, TILs isolated from tumor samples were studied in the earliest trials of ACT conducted at the surgical branch of the National Cancer Institute (NCI) in 1988 (29,30). At that time, objective responses were observed in 11 out of 20 patients with metastatic melanoma.…”

Section: Why Do Tils Have Variable Efficacy In the Treatmeant Of Soli...mentioning

confidence: 99%

Why do tumor-infiltrating lymphocytes have variable efficacy in the treatment of solid tumors?

2022

Front. Immunol.

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Lymphocytes in tumor tissue are called tumor-infiltrating lymphocytes (TILs), and they play a key role in the control and treatment of tumor diseases. Since the discovery in 1987 that cultured TILs can kill tumor cells more than 100 times more effectively than T-cells cultured from peripheral blood in melanoma, it has been confirmed that cultured TILs can successfully cure clinical patients with melanoma. Since 1989, after we investigated TIL isolation performance from solid tumors, we modified some procedures to increase efficacy, and thus successfully established new TIL isolation and culture methods in 1994. Moreover, our laboratory and clinicians using our cultured TILs have published more than 30 papers. To improve the efficacy of TILs, we have been carrying out studies of TIL efficacy to treat solid tumor diseases for approximately 30 years. The three main questions of TIL study have been “How do TILs remain silent in solid tumor tissue?”, “How do TILs attack homologous and heterologous antigens from tumor cells of solid tumors?”, and “How do TILs infiltrate solid tumor tissue from a distance into tumor sites to kill tumor cells?”. Research on these three issues has increasingly answered these questions. In this review I summarize the main issues surrounding TILs in treating solid tumors. This review aims to study the killing function of TILs from solid tumor tissues, thereby ultimately introducing the optimal strategy for patients suffering from solid tumors through personalized immunotherapy in the near future.

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Section: Why Do Tils Have Variable Efficacy In the Treatmeant Of Soli...mentioning

confidence: 99%

Why do tumor-infiltrating lymphocytes have variable efficacy in the treatment of solid tumors?

2022

Front. Immunol.

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“…Unfortunately, these models are not fully appropriate, as human neoplastic cells are usually ectopically injected in immunocompromised animals to avoid xenogeneic reaction [18][19][20][21][22][23][24][25][26]. Furthermore, some side effects of the immunotherapy, such as capillary leakage syndrome, have not been detected in animals [1][2][3][4][5][6]. The implant of patient derived xenograft tissue (PDX) in non-obese diabetic severe combined immunodeficient gamma (NOD-SCIDγ or NSG) mice has been extensively used [18,22,24].…”

Section: Tumor Cell Spheroids As a 3d Model To Study Tumor Cell Biology And Tumor-natural Killer Cross-talkmentioning

confidence: 99%

“…In late 1980s, the seminal findings of Rosenberg and colleagues on the so-called lymphokine activated killer (LAK) cells have shown that LAK-killing of tumor cells can eliminate both autologous and heterologous tumor cells in vitro, and cure mice from melanoma [1][2][3][4]. The transfer to the clinic of Rosenberg's findings by the systemic administration of interleukin 2 (IL2) showed several drawbacks, such as the capillary leakage syndrome [5,6] leading to fatal outcome in some patients [6].…”

Section: Introductionmentioning

confidence: 99%

“…The transfer to the clinic of Rosenberg's findings by the systemic administration of interleukin 2 (IL2) showed several drawbacks, such as the capillary leakage syndrome [5,6] leading to fatal outcome in some patients [6]. Indeed, IL2, essential for the generation of LAK cells, gave rise to relevant, unpredictable adverse effects in humans, not affecting murine models [1][2][3][4][5][6]. More recently, the key role of the immune response became evident testing immune-checkpoint (IC) blockers (B) to reactivate the anti-tumor immune response in host bearing tumors [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages

Poggi

Villa

Fernadez

et al. 2021

Cancers

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Several approaches have shown that the immune response against tumors strongly affects patients’ clinical outcome. Thus, the study of anti-tumor immunity is critical to understand and potentiate the mechanisms underlying the elimination of tumor cells. Natural killer (NK) cells are members of innate immunity and represent powerful anti-tumor effectors, able to eliminate tumor cells without a previous sensitization. Thus, the study of their involvement in anti-tumor responses is critical for clinical translation. This analysis has been performed in vitro, co-incubating NK with tumor cells and quantifying the cytotoxic activity of NK cells. In vivo confirmation has been applied to overcome the limits of in vitro testing, however, the innate immunity of mice and humans is different, leading to discrepancies. Different activating receptors on NK cells and counter-ligands on tumor cells are involved in the antitumor response, and innate immunity is strictly dependent on the specific microenvironment where it takes place. Thus, three-dimensional (3D) culture systems, where NK and tumor cells can interact in a tissue-like architecture, have been created. For example, tumor cell spheroids and primary organoids derived from several tumor types, have been used so far to analyze innate immune response, replacing animal models. Herein, we briefly introduce NK cells and analyze and discuss in detail the properties of 3D tumor culture systems and their use for the study of tumor cell interactions with NK cells.

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“…Following publication of the original article (Rosenberg et al 2021 ), the editorial team requested to change the article title as the author Steven A. Rosenberg received the journal Cerami award.…”

Section: Correction To: Mol Med (2021) 27:63 Https://doiorg/101186/s10020-021-00321-3mentioning

confidence: 99%

A Journey in Science: Immersion in the search for effective cancer immunotherapies

Cited by 10 publications

References 88 publications

Why do tumor-infiltrating lymphocytes have variable efficacy in the treatment of solid tumors?

Why do tumor-infiltrating lymphocytes have variable efficacy in the treatment of solid tumors?

Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages

Correction to: A Journey in Science: Immersion in the search for effective cancer immunotherapies

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