Passage Proteins Known as Cancer/testis Antigens (CTAs) Are Normally Expressed Exclusively

Passage
Proteins known as cancer/testis antigens (CTAs) are normally expressed exclusively in germline cells but may become reactivated in cancer cells due to chromatin remodeling (eg, gene activation due to DNA demethylation) .  Because of their normally restricted expression, CTAs can elicit an immune response when expressed by cancer cells derived from other tissue types.  Several CTAs are known to inhibit apoptosis or promote cell division in cancer cells, making them more resistant to traditional chemotherapy.  Accordingly, cancer research instead has focused on immunotherapy treatments targeting CTAs.In a study, researchers isolated peripheral blood lymphocytes (B lymphocytes, T lymphocytes, natural killer [NK] cells) from two healthy individuals.  These lymphocytes were cultured with signaling factors known to promote helper T cell (T_h cell) proliferation.  After 7 days, cultures from both individuals were enriched for T_h cells, which expressed proteins generally involved in activating other lymphocytes.  A subset of the cultures from each individual was treated with 5-Aza-CdR, a DNA-demethylating agent.  Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze expression of several CTAs (ie, MAGEs) in both untreated and 5-Aza-CdR-treated lymphocyte cultures, as well as in untreated melanoma (skin cancer) and breast cancer cell lines (Figure 1) .  GAPDH, a protein expressed in most cell types, served as a control.
Figure 1  Gels showing RT-PCR results for MAGE expressionAdditional peripheral blood lymphocytes were isolated from the same healthy individuals and incubated with the T_h cells that had been treated with 5-Aza-CdR.  After 11 days, these cultures consisted primarily of an increased number of NK cells and cytotoxic T lymphocytes (CTLs) .  Researchers found that these CTLs were able to induce apoptosis in breast cancer cell lines but did not affect healthy cells.Researchers used a similar procedure to induce CTL proliferation in lymphocytes isolated from a breast cancer patient.  The CTLs were then incubated with cells obtained from a biopsy of the patient's cancerous tissue.  Following this experiment, researchers found that apoptosis was induced in the patient's cancer cells.
Kirkin et al. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nature Communications. 2018; 9:785
-CTLs incubated in the absence of 5-Aza-CdR-treated T_h cells were unable to induce apoptosis in the cancer cells described in the passage.  Given this, which of the following statements best describes why the 5-Aza-CdR-treated T_h cells were necessary to induce proliferation of functional CTLs?

A) CTLs are activated by signals from cancerous cells.
B) CTLs that induce apoptosis in healthy cells are eliminated by T_h cells.
C) CTLs must receive signals from other immune cells to become activated.
D) CTLs require signals from T_h cells to express antigenic proteins.

Correct Answer:

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