According to the study, how do the transformed cancer
cells contribute to the immune system's response against
cancer?

Question

Stanford Medicine scientists transform cancer cells
into weapons against cancer
March 1, 2023 - By Christopher Vaughan
(1º§) Some cities fight gangs with ex-members who  educate kids and starve gangs of new recruits. Stanford
Medicine researchers have done something similar with
cancer — altering cancer cells so that they teach the
body's immune system to fight the very cancer the cells
came from.
(2º§) "This approach could open up an entirely new
therapeutic approach to treating cancer," said Ravi
Majeti, MD, PhD, a professor of hematology and the
study's senior author. The research was published March
 1 in Cancer Discovery. The lead author is Miles Linde,
PhD, a former PhD student in immunology who is now at
the Fred Hutchinson Cancer Institute in Seattle.
(3º§) Some of the most promising cancer treatments use
the patient's own immune system to attack the cancer,
often __ taking the brakes off immune responses to
cancer or by teaching the immune system to recognize
and attack the cancer more vigorously. T cells, part of the
immune system that learns to identify and attack new
pathogens such as viruses, can be trained to recognize
specific cancer antigens, which are proteins that
generate an immune response.
(4º§) For instance, in CAR T-cell therapy, T cells are
taken from a patient, programmed to recognize a specific
cancer antigen, then returned to the patient. But there are
many cancer antigens, and physicians sometimes need
 to guess which ones will be most potent.
(5º§) A better approach would be to train T cells to
recognize cancer via processes that more closely mimic
the way things naturally occur in the body — like the way
 a vaccine teaches the immune system to recognize
pathogens. T cells learn to recognize pathogens because
special antigen presenting cells (APCs) gather pieces of
the pathogen and show them to the T cells in a way that
tells the T cells, "Here is what the pathogen looks like —
go get it."
(6º§) Something similar in cancer would be for APCs to
gather up the many antigens that characterize a cancer
cell. That way, instead of T cells being programmed to
attack one or a few antigens, they are trained to
recognize many cancer antigens and are more likely to
wage a multipronged attack on the cancer.
(7º§) Now that researchers have become adept at
transforming one kind of cell into another, Majeti and his
colleagues had a hunch that if they turned cancer cells
into a type of APC called macrophages, they would be
naturally adept at teaching T cells what to attack.
(8º§) "We hypothesized that maybe cancer cells
reprogrammed into macrophage cells could stimulate T
cells because those APCs carry all the antigens of the
cancer cells they came from," said Majeti, who is also the
RZ Cao Professor, assistant director of the Institute for
Stem Cell Biology and Regenerative Medicine and
director of the Ludwig Center for Cancer Stem Cell
Research and Medicine.
(9º§) The study builds on prior research from the Majeti
lab showing that cells taken from patients with a type of
acute leukemia could be converted into non-leukemic
macrophages with many of the properties of APCs.(10º§) In the current study, the researchers programmed
mouse leukemia cells so that some of them could be
induced to transform themselves into APCs. When they
tested their cancer vaccine strategy on the mouse
immune system, the mice successfully cleared the
cancer.
(11º§) "When we first saw the data showing clearance of
the leukemia in the mice __ working immune systems, we were blown away," Majeti said. "We couldn't believe it
worked as well as it did."
(12º§) Other experiments showed that the cells created
from cancer cells were indeed acting as
antigen-presenting cells that sensitized T cells to the
cancer. "What's more, we showed that the immune
system remembered what these cells taught them,"
Majeti said. "When we reintroduced cancer to these mice
over 100 days after the initial tumor inoculation, they still
had a strong immunological response that protected
them."
(13º§) "We wondered, If this works with leukemias, will it
also work with solid tumors?" Majeti said. The team
tested the same approach using mouse fibrosarcoma,
breast cancer, and bone cancer. "The transformation of
cancer cells from solid tumors was not as efficient, but we
still observed positive results," Majeti said. With all three
cancers, the creation of tumor-derived APCs led to
significantly improved survival.
(14º§) Lastly, the researchers returned to the original
type of acute leukemia. When the human leukemia
cell-derived APCs were exposed to human T cells from
the same patient, they observed all the signs that would
be expected if the APCs were indeed teaching the T cells
how to attack the leukemia.
(15º§) "We showed that reprogrammed tumor cells could
lead to a durable and systemic attack on the cancer in
mice and a similar response with human patient immune
cells," Majeti said. "In the future we might be able to take
out tumor cells, transform them into APCs and give them
back to patients as a therapeutic cancer vaccine."
(16º§) "Ultimately, we might be able to inject RNA into
patients and transform enough cells to activate the
immune system against cancer without having to take
cells out first," Majeti said. "That's science fiction __ this
point, but that's the direction we are interested in going."
(17º§) The work was supported by funding from the
Ludwig Foundation for Cancer Research, the Emerson
Collective Cancer Research Fund, the New York Stem
Cell Foundation, the Stinehart-Reed Foundation, the
Leukemia and Lymphoma Society, the J. Benjamin
Eckenhoff Fund, the Blavatnik Family Fellowship, the
Deutsche Forschungsgemainshaft, the Knut and Alice
Wallenberg Foundation, the Stanford Human Biology
Research Exploration Program, the National Institutes of
Health (grant F31CA196029), the American Society of
Hematology, the A.P. Giannini Foundation, and the
Stanford Cancer Institute.
(adapted)
med.stanford.edu/news/all-news/2023/03/cancer-hematology.html
PROFESSOR INGLÊS - 1 8 According to the study, how do the transformed cancer
cells contribute to the immune system's response against
cancer? Alternativa A: By suppressing T cell activity. Ou Alternativa B: By training T cells to recognize multiple cancer
antigens. Ou Alternativa C: Through the introduction of external immune cells. Ou Alternativa D: By directly attacking cancer cells.

Qconcursos · Accepted Answer

Alternativa [B] By training T cells to recognize multiple cancer
antigens. Tema central: A questão avalia a compreensão leitora, principalmente sobre o funcionamento de uma nova estratégia terapêutica contra o câncer baseada na imunologia: a transformação de células cancerígenas em ferramentas para estimular a resposta do sistema imune contra a própria doença.

Explicação didática: O texto relata uma inovação biotecnológica na qual pesquisadores de Stanford reprogramam células cancerígenas para que elas se tornem células apresentadoras de antígenos (APCs, como os macrófagos). Essas APCs têm um papel fundamental na imunidade: apresentam múltiplos antígenos das células tumorais às células T, treinando essas células do sistema imunológico a reconhecer e atacar o câncer de maneira orientada e eficiente.

Justificativa da alternativa correta (B):
A B) By training T cells to recognize multiple cancer antigens coincide perfeitamente com o procedimento descrito no texto. Destaca-se o trecho: “instead of T cells being programmed to attack one or a few antigens, they are trained to recognize many cancer antigens and are more likely to wage a multipronged attack on the cancer”. Ou seja, as células T passam a identificar diversos antígenos, o que torna a resposta imune mais ampla e potente.

Análise das alternativas incorretas:

A) By suppressing T cell activity.
  Errado. O texto trata de estimular, não suprimir, a ação das células T.
  C) Through the introduction of external immune cells.
  Incorreto. A estratégia não envolve a adição de células de outra procedência, mas sim a reprogramação de células do próprio tumor.
  D) By directly attacking cancer cells.
  Impreciso. As células reprogramadas não destroem o câncer diretamente; elas orientam as células T para que realizem o ataque.

Estratégias para questões semelhantes:
Busque palavras-chave como train, recognize, antigens, multiply e avalie se a ação é direta ou mediada pelo sistema imune. Atenção para não confundir mecanismos de ação (estimulação imunológica) com resultados finais (ataque direto ao câncer) ou processos externos (adição de células externas).

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